Inheritance of nesting behaviour across natural environmental variation in a turtle with temperature-dependent sex determination.

PubMed

McGaugh, Suzanne E; Schwanz, Lisa E; Bowden, Rachel M; Gonzalez, Julie E; Janzen, Fredric J

2010-04-22

Nesting behaviour is critical for reproductive success in oviparous organisms with no parental care. In organisms where sex is determined by incubation temperature, nesting behaviour may be a prime target of selection in response to unbalanced sex ratios. To produce an evolutionary change in response to sex-ratio selection, components of nesting behaviour must be heritable. We estimated the field heritability of two key components of nesting behaviour in a population of painted turtles (Chrysemys picta) with temperature-dependent sex determination by applying the 'animal model' to a pedigree reconstructed from genotype data. We obtained estimates of low to non-detectable heritability using repeated records across all environments. We then determined environment-specific heritability by grouping records with similar temperatures for the winter preceding the nesting season, a variable known to be highly associated with our two traits of interest, nest vegetation cover and Julian date of nesting. The heritability estimates of nest vegetation cover and Julian date of nesting were qualitatively highest and significant, or nearly so, after hot winters. Additive genetic variance for these traits was not detectable after cold winters. Our analysis suggests that the potential for evolutionary change of nesting behaviour may be dependent on the thermal conditions of the preceding winter, a season that is predicted to be especially subject to climate change.

Effect of Body Composition Methodology on Heritability Estimation of Body Fatness

PubMed Central

Elder, Sonya J.; Roberts, Susan B.; McCrory, Megan A.; Das, Sai Krupa; Fuss, Paul J.; Pittas, Anastassios G.; Greenberg, Andrew S.; Heymsfield, Steven B.; Dawson-Hughes, Bess; Bouchard, Thomas J.; Saltzman, Edward; Neale, Michael C.

2014-01-01

Heritability estimates of human body fatness vary widely and the contribution of body composition methodology to this variability is unknown. The effect of body composition methodology on estimations of genetic and environmental contributions to body fatness variation was examined in 78 adult male and female monozygotic twin pairs reared apart or together. Body composition was assessed by six methods – body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold thickness. Body fatness was expressed as percent body fat, fat mass, and fat mass/height2 to assess the effect of body fatness expression on heritability estimates. Model-fitting multivariate analyses were used to assess the genetic and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8–43.4 kg/m2). There was a significant effect of body composition methodology (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%) and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body fatness as percent body fat resulted in significantly higher heritability estimates (on average 10.3% higher) compared to expression as fat mass/height2 (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave the least biased heritability assessments, based on the small contribution of specific genetic factors to their genetic variance. A model combining DXA and TBW methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and significant contributions of common and unique environmental factors (22% and 18%, respectively). The body fatness heritability estimate of 60% indicates a smaller contribution of genetic variance to total variance than many previous studies using less powerful research designs have indicated. The results also highlight the importance of environmental factors and possibly genotype by environmental interactions in the etiology of weight gain and the obesity epidemic. PMID:25067962

Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits

PubMed Central

Zaitlen, Noah; Kraft, Peter; Patterson, Nick; Pasaniuc, Bogdan; Bhatia, Gaurav; Pollack, Samuela; Price, Alkes L.

2013-01-01

Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays. PMID:23737753

Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits.

PubMed

Zaitlen, Noah; Kraft, Peter; Patterson, Nick; Pasaniuc, Bogdan; Bhatia, Gaurav; Pollack, Samuela; Price, Alkes L

2013-05-01

Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.

Genetic support for the dual nature of attention deficit hyperactivity disorder: substantial genetic overlap between the inattentive and hyperactive-impulsive components.

PubMed

McLoughlin, Gráinne; Ronald, Angelica; Kuntsi, Jonna; Asherson, Philip; Plomin, Robert

2007-12-01

Attention deficit hyperactivity disorder (ADHD) is a common, complex and highly heritable disorder, characterised by inattentive, impulsive and overactive behaviour. Evidence for the heritability of ADHD measures in twin population samples has come from the analysis of total scores that combine inattentive and hyperactive-impulsive symptoms subscales. This study investigated, in a community sample, the aetiology of ADHD-like traits and the aetiological overlap between the two dimensions that define the ADHD disorder. Parents of 6,222 approximately 8-year-old twin pairs from the Twins Early Development Study (TEDS) population sample completed the two subscales of the Conners' 18-item DSMIV checklist, a screening instrument for ADHD symptoms. Both subscales were highly heritable (hyperactive-impulsive: 88%; inattentive: 79%). Bivariate genetic modelling indicated substantial genetic overlap between the two components; however, there were significant independent genetic effects. These findings suggest that many genes associated with the hyperactivity-impulsivity dimension will also be associated with the inattentive dimension but that there is significant genetic heterogeneity as well. These results provide genetic support for combining the two behavioural dimensions that define ADHD, but also suggest that some symptom-specific genes will also be identified.

Integrating Multiple Correlated Phenotypes for Genetic Association Analysis by Maximizing Heritability

PubMed Central

Zhou, Jin J.; Cho, Michael H.; Lange, Christoph; Lutz, Sharon; Silverman, Edwin K.; Laird, Nan M.

2015-01-01

Many correlated disease variables are analyzed jointly in genetic studies in the hope of increasing power to detect causal genetic variants. One approach involves assessing the relationship between each phenotype and each single nucleotide polymorphism (SNP) individually and using a Bonferroni correction for the effective number of tests conducted. Alternatively, one can apply a multivariate regression or a dimension reduction technique, such as principal component analysis (PCA), and test for the association with the principal components (PC) of the phenotypes rather than the individual phenotypes. Inspired by the previous approaches of combining phenotypes to maximize heritability at individual SNPs, in this paper, we propose to construct a maximally heritable phenotype (MaxH) by taking advantage of the estimated total heritability and co-heritability. The heritability and co-heritability only need to be estimated once, therefore our method is applicable to genome-wide scans. MaxH phenotype is a linear combination of the individual phenotypes with increased heritability and power over the phenotypes being combined. Simulations show that the heritability and power achieved agree well with the theory for large samples and two phenotypes. We compare our approach with commonly used methods and assess both the heritability and the power of the MaxH phenotype. Moreover we provide suggestions for how to choose the phenotypes for combination. An application of our approach to a COPD genome-wide association study shows the practical relevance. PMID:26111731

Heritability estimates of the Big Five personality traits based on common genetic variants.

PubMed

Power, R A; Pluess, M

2015-07-14

According to twin studies, the Big Five personality traits have substantial heritable components explaining 40-60% of the variance, but identification of associated genetic variants has remained elusive. Consequently, knowledge regarding the molecular genetic architecture of personality and to what extent it is shared across the different personality traits is limited. Using genomic-relatedness-matrix residual maximum likelihood analysis (GREML), we here estimated the heritability of the Big Five personality factors (extraversion, agreeableness, conscientiousness, neuroticism and openness for experience) in a sample of 5011 European adults from 527,469 single-nucleotide polymorphisms across the genome. We tested for the heritability of each personality trait, as well as for the genetic overlap between the personality factors. We found significant and substantial heritability estimates for neuroticism (15%, s.e. = 0.08, P = 0.04) and openness (21%, s.e. = 0.08, P < 0.01), but not for extraversion, agreeableness and conscientiousness. The bivariate analyses showed that the variance explained by common variants entirely overlapped between neuroticism and openness (rG = 1.00, P < 0.001), despite low phenotypic correlation (r = - 0.09, P < 0.001), suggesting that the remaining unique heritability may be determined by rare or structural variants. As far as we are aware of, this is the first study estimating the shared and unique heritability of all Big Five personality traits using the GREML approach. Findings should be considered exploratory and suggest that detectable heritability estimates based on common variants is shared between neuroticism and openness to experiences.

Heritability of female extra-pair paternity rate in song sparrows (Melospiza melodia)

PubMed Central

Reid, Jane M.; Arcese, Peter; Sardell, Rebecca J.; Keller, Lukas F.

2011-01-01

The forces driving the evolution of extra-pair reproduction in socially monogamous animals remain widely debated and unresolved. One key hypothesis is that female extra-pair reproduction evolves through indirect genetic benefits, reflecting increased additive genetic value of extra-pair offspring. Such evolution requires that a female's propensity to produce offspring that are sired by an extra-pair male is heritable. However, additive genetic variance and heritability in female extra-pair paternity (EPP) rate have not been quantified, precluding accurate estimation of the force of indirect selection. Sixteen years of comprehensive paternity and pedigree data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) showed significant additive genetic variance and heritability in the proportion of a female's offspring that was sired by an extra-pair male, constituting major components of the genetic architecture required for extra-pair reproduction to evolve through indirect additive genetic benefits. However, estimated heritabilities were moderately small (0.12 and 0.18 on the observed and underlying latent scales, respectively). The force of selection on extra-pair reproduction through indirect additive genetic benefits may consequently be relatively weak. However, the additive genetic variance and non-zero heritability observed in female EPP rate allow for multiple further genetic mechanisms to drive and constrain mating system evolution. PMID:20980302

Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study.

PubMed

North, Kari E; Howard, Barbara V; Welty, Thomas K; Best, Lyle G; Lee, Elisa T; Yeh, J L; Fabsitz, Richard R; Roman, Mary J; MacCluer, Jean W

2003-02-15

The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study (conducted between 1998 and 1999) and evaluate the heritabilities of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes.

Cross-Tissue and Tissue-Specific eQTLs: Partitioning the Heritability of a Complex Trait

PubMed Central

Torres, Jason M.; Gamazon, Eric R.; Parra, Esteban J.; Below, Jennifer E.; Valladares-Salgado, Adan; Wacher, Niels; Cruz, Miguel; Hanis, Craig L.; Cox, Nancy J.

2014-01-01

Top signals from genome-wide association studies (GWASs) of type 2 diabetes (T2D) are enriched with expression quantitative trait loci (eQTLs) identified in skeletal muscle and adipose tissue. We therefore hypothesized that such eQTLs might account for a disproportionate share of the heritability estimated from all SNPs interrogated through GWASs. To test this hypothesis, we applied linear mixed models to the Wellcome Trust Case Control Consortium (WTCCC) T2D data set and to data sets representing Mexican Americans from Starr County, TX, and Mexicans from Mexico City. We estimated the proportion of phenotypic variance attributable to the additive effect of all variants interrogated in these GWASs, as well as a much smaller set of variants identified as eQTLs in human adipose tissue, skeletal muscle, and lymphoblastoid cell lines. The narrow-sense heritability explained by all interrogated SNPs in each of these data sets was substantially greater than the heritability accounted for by genome-wide-significant SNPs (∼10%); GWAS SNPs explained over 50% of phenotypic variance in the WTCCC, Starr County, and Mexico City data sets. The estimate of heritability attributable to cross-tissue eQTLs was greater in the WTCCC data set and among lean Hispanics, whereas adipose eQTLs significantly explained heritability among Hispanics with a body mass index ≥ 30. These results support an important role for regulatory variants in the genetic component of T2D susceptibility, particularly for eQTLs that elicit effects across insulin-responsive peripheral tissues. PMID:25439722

Heritability construction for provenance and family selection

Treesearch

Fan H. Kung; Calvin F. Bey

1977-01-01

Concepts and procedures for heritability estimations through the variance components and the unified F-statistics approach are described. The variance components approach is illustrated by five possible family selection schemes within a diallel mating test, while the unified F-statistics approach is demonstrated by a geographic variation study. In a balance design, the...

Genetic Architecture of Lacunar Stroke.

PubMed

Traylor, Matthew; Bevan, Steve; Baron, Jean-Claude; Hassan, Ahamad; Lewis, Cathryn M; Markus, Hugh S

2015-09-01

Lacunar strokes comprise ≈20% of all strokes. Despite this frequency, their pathogenesis is poorly understood. Previous genome-wide association studies in lacunar stroke have been disappointing, which may be because of phenotypic heterogeneity. Pathological and radiological studies suggest that there may be different pathologies underlying lacunar strokes. This has led to the suggestion of 2 subtypes: isolated lacunar infarcts and multiple lacunar infarcts and leukoaraiosis. We performed genome-wide analyses in a magnetic resonance imaging-verified cohort of 1012 younger onset lacunar stroke cases and 964 controls. Using these data, we first estimated the heritability of lacunar stroke and its 2 hypothesized subtypes, and secondly, we determined whether this is enriched for regulatory regions in the genome, as defined by data from Encyclopedia of DNA Elements (ENCODE) and other sources. Finally, we determine the evidence for a polygenic contribution from rare variation to lacunar stroke and its subtypes. Our results indicate a substantial heritable component to magnetic resonance imaging-verified lacunar stroke (20%-25%) and its 2 subtypes (isolated lacunar infarct, 15%-18%; multiple lacunar infarcts/leukoaraiosis, 23%-28%). This heritable component is significantly enriched for sites affecting expression of genes. In addition, we show that the risk of the 2 subtypes of lacunar stroke in isolation, but not in combination, is associated with rare variation in the genome. Lacunar stroke, when defined on magnetic resonance imaging, is a highly heritable complex disease. Much of this heritability arises from regions of the genome affecting gene regulation. Rare variation affects 2 subtypes of lacunar in isolation, suggesting that they may have distinct genetic susceptibility factors. © 2015 The Authors.

Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

PubMed Central

Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

2014-01-01

IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE This is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I-association within families that is consistent with expectations from case-control studies. Together these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder. PMID:24522887

Modeling genetic and environmental factors to increase heritability and ease the identification of candidate genes for birth weight: a twin study.

PubMed

Gielen, M; Lindsey, P J; Derom, C; Smeets, H J M; Souren, N Y; Paulussen, A D C; Derom, R; Nijhuis, J G

2008-01-01

Heritability estimates of birth weight have been inconsistent. Possible explanations are heritability changes during gestational age or the influence of covariates (e.g. chorionicity). The aim of this study was to model birth weights of twins across gestational age and to quantify the genetic and environmental components. We intended to reduce the common environmental variance to increase heritability and thereby the chance of identifying candidate genes influencing the genetic variance of birth weight. Perinatal data were obtained from 4232 live-born twin pairs from the East Flanders Prospective Twin Survey, Belgium. Heritability of birth weights across gestational ages was estimated using a non-linear multivariate Gaussian regression with covariates in the means model and in covariance structure. Maternal, twin-specific, and placental factors were considered as covariates. Heritability of birth weight decreased during gestation from 25 to 42 weeks. However, adjusting for covariates increased the heritability over this time period, with the highest heritability for first-born twins of multipara with separate placentas, who were staying alive (from 52% at 25 weeks to 30% at 42 weeks). Twin-specific factors revealed latent genetic components, whereas placental factors explained common and unique environmental factors. The number of placentas and site of the insertion of the umbilical cord masked the effect of chorionicity. Modeling genetic and environmental factors leads to a better estimate of their role in growth during gestation. For birth weight, mainly environmental factors were explained, resulting in an increase of the heritability and thereby the chance of finding genes influencing birth weight in linkage and association studies.

Genetic architecture of lipid traits changes over time and differs by race: Princeton Lipid Follow-up Study.

PubMed

Woo, Jessica G; Morrison, John A; Stroop, Davis M; Aronson Friedman, Lisa; Martin, Lisa J

2014-07-01

Dyslipidemia is a major risk factor for CVD. Previous studies on lipid heritability have largely focused on white populations assessed after the obesity epidemic. Given secular trends and racial differences in lipid levels, this study explored whether lipid heritability is consistent across time and between races. African American and white nuclear families had fasting lipids measured in the 1970s and 22-30 years later. Heritability was estimated, and bivariate analyses between visits were conducted by race using variance components analysis. A total of 1,454 individuals (age 14.1/40.6 for offspring/parents at baseline; 39.6/66.5 at follow-up) in 373 families (286 white, 87 African American) were included. Lipid trait heritabilities were typically stronger during the 1970s than the 2000s. At baseline, additive genetic variation for LDL was significantly lower in African Americans than whites (P = 0.015). Shared genetic contribution to lipid variability over time was significant in both whites (all P < 0.0001) and African Americans (P ≤ 0.05 for total, LDL, and HDL cholesterol). African American families demonstrated shared environmental contributions to lipid variation over time (all P ≤ 0.05). Lower heritability, lower LDL genetic variance, and durable environmental effects across the obesity epidemic in African American families suggest race-specific approaches are needed to clarify the genetic etiology of lipids. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Shared genetic contributions of fruit and vegetable consumption with BMI in families 20 y after sharing a household.

PubMed

Martin, Lisa J; Lee, Seung-Yeon; Couch, Sarah C; Morrison, John; Woo, Jessica G

2011-10-01

Obesity has a strong genetic basis, but the identification of genetic variants has not resulted in improved clinical care. However, phenotypes that influence weight, such as diet, may have shared underpinnings with obesity. Interestingly, diet also has a genetic basis. Thus, we hypothesized that the genetic underpinnings of diet may partially overlap with the genetics of obesity. Our objective was to determine whether dietary intake and BMI share heritable components in adulthood. We used a cross-sectional cohort of parents and adult offspring (n = 1410) from the Princeton Follow-up Study. Participants completed Block food-frequency questionnaires 15-27 y after sharing a household. Heritability of dietary intakes was estimated by using variance components analysis. Bivariate genetic analyses were used to estimate the shared effects between BMI and heritable dietary intakes. Fruit, vegetable, and protein consumption exhibited moderate heritability [(mean ± SE) 0.26 ± 0.06, 0.32 ± 0.06, and 0.21 ± 0.06, respectively; P < 0.001], but other dietary intakes were modest (h(2) < 0.2). Only fruit and vegetable consumption exhibited genetic correlations with BMI (ρ(g) = -0.28 ± 0.13 and -0.30 ± 0.13, respectively; P < 0.05). Phenotypic correlations with BMI were not significant. We showed that fruit, vegetable, and protein intakes are moderately heritable and that fruit and vegetable consumption shares underlying genetic effects with BMI in adulthood, which suggests that individuals genetically predisposed to low fruit and vegetable consumption may be predisposed to higher BMI. Thus, obese individuals who have low fruit and vegetable consumption may require targeted interventions that go beyond low-calorie, plant-based programs for weight management.

Heritability of myopia and ocular biometrics in Koreans: the healthy twin study.

PubMed

Kim, Myung Hun; Zhao, Di; Kim, Woori; Lim, Dong-Hui; Song, Yun-Mi; Guallar, Eliseo; Cho, Juhee; Sung, Joohon; Chung, Eui-Sang; Chung, Tae-Young

2013-05-01

To estimate the heritabilities of myopia and ocular biometrics among different family types among a Korean population. We studied 1508 adults in the Healthy Twin Study. Spherical equivalent, axial length, anterior chamber depth, and corneal astigmatism were measured by refraction, corneal topography, and A-scan ultrasonography. To see the degree of resemblance among different types of family relationships, intraclass correlation coefficients (ICC) were calculated. Variance-component methods were applied to estimate the genetic contributions to eye phenotypes as heritability based on the maximum likelihood estimation. Narrow sense heritability was calculated as the proportion of the total phenotypic variance explained by additive genetic effects, and linear and nonlinear effects of age, sex, and interactions between age and sex were adjusted. A total of 240 monozygotic twin pairs, 45 dizygotic twin pairs, and 938 singleton adult family members who were first-degree relatives of twins in 345 families were included in the study. ICCs for spherical equivalent from monozygotic twins, pooled first-degree pairs, and spouse pairs were 0.83, 0.34, and 0.20, respectively. The ICCs of other ocular biometrics were also significantly higher in monozygotic twins compared with other relative pairs, with greater consistency and conformity. The estimated narrow sense heritability (95% confidence interval) was 0.78 (0.71-0.84) for spherical equivalent; 0.86 (0.82-0.90) for axial length; 0.83 (0.76-0.91) for anterior chamber depth; and 0.70 (0.63-0.77) for corneal astigmatism. The estimated heritability of spherical equivalent and ocular biometrics in the Korean population suggests the compelling evidence that all traits are highly heritable.

Genetics of attention deficit hyperactivity disorder.

PubMed

Faraone, Stephen V; Larsson, Henrik

2018-06-11

Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.

An analysis of indirect genetic effects on adult body weight of the Pacific white shrimp Litopenaeus vannamei at low rearing density.

PubMed

Luan, Sheng; Luo, Kun; Chai, Zhan; Cao, Baoxiang; Meng, Xianhong; Lu, Xia; Liu, Ning; Xu, Shengyu; Kong, Jie

2015-12-14

Our aim was to estimate the genetic parameters for the direct genetic effect (DGE) and indirect genetic effects (IGE) on adult body weight in the Pacific white shrimp. IGE is the heritable effect of an individual on the trait values of its group mates. To examine IGE on body weight, 4725 shrimp from 105 tagged families were tested in multiple small test groups (MSTG). Each family was separated into three groups (15 shrimp per group) that were randomly assigned to 105 concrete tanks with shrimp from two other families. To estimate breeding values, one large test group (OLTG) in a 300 m(2) circular concrete tank was used for the communal rearing of 8398 individuals from 105 families. Body weight was measured after a growth-test period of more than 200 days. Variance components for body weight in the MSTG programs were estimated using an animal model excluding or including IGE whereas variance components in the OLTG programs were estimated using a conventional animal model that included only DGE. The correlation of DGE between MSTG and OLTG programs was estimated by a two-trait animal model that included or excluded IGE. Heritability estimates for body weight from the conventional animal model in MSTG and OLTG programs were 0.26 ± 0.13 and 0.40 ± 0.06, respectively. The log likelihood ratio test revealed significant IGE on body weight. Total heritable variance was the sum of direct genetic variance (43.5%), direct-indirect genetic covariance (2.1%), and indirect genetic variance (54.4%). It represented 73% of the phenotypic variance and was more than two-fold greater than that (32%) obtained by using a classical heritability model for body weight. Correlations of DGE on body weight between MSTG and OLTG programs were intermediate regardless of whether IGE were included or not in the model. Our results suggest that social interactions contributed to a large part of the heritable variation in body weight. Small and non-significant direct-indirect genetic correlations implied that neutral or slightly cooperative heritable interactions, rather than competition, were dominant in this population but this may be due to the low rearing density.

Heritability and intrafamilial aggregation of arterial characteristics.

PubMed

Seidlerová, Jitka; Bochud, Murielle; Staessen, Jan A; Cwynar, Marcin; Dolejsová, Milena; Kuznetsova, Tatiana; Nawrot, Tim; Olszanecka, Agnieszka; Stolarz, Katarzyna; Thijs, Lutgarde; Wojciechowska, Wiktoria; Struijker-Boudier, Harry A; Kawecka-Jaszcz, Kalina; Elston, Robert C; Fagard, Robert; Filipovský, Jan

2008-04-01

We investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components. Using a family-based population sample, we recruited 204 parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the Czech Republic (50). We measured peripheral pulse pressure (PPp) sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs) by applanation tonometry at the radial artery; and aortic pulse wave velocity (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively. We found significant heritability for PAIx, CAIx, PPc and mean arterial pressure ranging from 0.37 to 0.41; P < or = 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r > or = 0.12; P < or = 0.02) with the exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic correlation between PWV and the other arterial indexes were significant (rhoG > or = 0.29; P < 0.0001). The corresponding environmental correlations were only significantly positive for PPp (rhoE = 0.10, P = 0.03). The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits.

Heritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample

PubMed Central

Lin, Bochao Danae; Mbarek, Hamdi; Willemsen, Gonneke; Dolan, Conor V.; Fedko, Iryna O.; Abdellaoui, Abdel; de Geus, Eco J.; Boomsma, Dorret I.; Hottenga, Jouke-Jan

2015-01-01

Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on hair color within a large cohort of twins, their parents and siblings from the Netherlands Twin Register (NTR). Self-reported hair color was analyzed as five binary phenotypes, namely “blond versus non-blond”, “red versus non-red”, “brown versus non-brown”, “black versus non-black”, and “light versus dark”. The broad-sense heritability of hair color was estimated between 73% and 99% and the genetic component included non-additive genetic variance. Assortative mating for hair color was significant, except for red and black hair color. From GCTA analyses, at most 24.6% of the additive genetic variance in hair color was explained by 1000G well-imputed SNPs. Genome-wide association analysis for each hair color showed that SNPs in the MC1R region were significantly associated with red, brown and black hair, and also with light versus dark hair color. Five other known genes (HERC2, TPCN2, SLC24A4, IRF4, and KITLG) gave genome-wide significant hits for blond, brown and light versus dark hair color. We did not find and replicate any new loci for hair color. PMID:26184321

Modeling the Covariance Structure of Complex Datasets Using Cognitive Models: An Application to Individual Differences and the Heritability of Cognitive Ability.

PubMed

Evans, Nathan J; Steyvers, Mark; Brown, Scott D

2018-06-05

Understanding individual differences in cognitive performance is an important part of understanding how variations in underlying cognitive processes can result in variations in task performance. However, the exploration of individual differences in the components of the decision process-such as cognitive processing speed, response caution, and motor execution speed-in previous research has been limited. Here, we assess the heritability of the components of the decision process, with heritability having been a common aspect of individual differences research within other areas of cognition. Importantly, a limitation of previous work on cognitive heritability is the underlying assumption that variability in response times solely reflects variability in the speed of cognitive processing. This assumption has been problematic in other domains, due to the confounding effects of caution and motor execution speed on observed response times. We extend a cognitive model of decision-making to account for relatedness structure in a twin study paradigm. This approach can separately quantify different contributions to the heritability of response time. Using data from the Human Connectome Project, we find strong evidence for the heritability of response caution, and more ambiguous evidence for the heritability of cognitive processing speed and motor execution speed. Our study suggests that the assumption made in previous studies-that the heritability of cognitive ability is based on cognitive processing speed-may be incorrect. More generally, our methodology provides a useful avenue for future research in complex data that aims to analyze cognitive traits across different sources of related data, whether the relation is between people, tasks, experimental phases, or methods of measurement. © 2018 Cognitive Science Society, Inc.

Volumetric mammographic density: heritability and association with breast cancer susceptibility loci.

PubMed

Brand, Judith S; Humphreys, Keith; Thompson, Deborah J; Li, Jingmei; Eriksson, Mikael; Hall, Per; Czene, Kamila

2014-12-01

Mammographic density is a strong heritable trait, but data on its genetic component are limited to area-based and qualitative measures. We studied the heritability of volumetric mammographic density ascertained by a fully-automated method and the association with breast cancer susceptibility loci. Heritability of volumetric mammographic density was estimated with a variance component model in a sib-pair sample (N pairs = 955) of a Swedish screening based cohort. Associations with 82 established breast cancer loci were assessed in an independent sample of the same cohort (N = 4025 unrelated women) using linear models, adjusting for age, body mass index, and menopausal status. All tests were two-sided, except for heritability analyses where one-sided tests were used. After multivariable adjustment, heritability estimates (standard error) for percent dense volume, absolute dense volume, and absolute nondense volume were 0.63 (0.06) and 0.43 (0.06) and 0.61 (0.06), respectively (all P < .001). Percent and absolute dense volume were associated with rs10995190 (ZNF365; P = 9.0 × 10(-6) and 8.9 × 10(-7), respectively) and rs9485372 (TAB2; P = 1.8 × 10(-5) and 1.8 × 10(-3), respectively). We also observed associations of rs9383938 (ESR1) and rs2046210 (ESR1) with the absolute dense volume (P = 2.6 × 10(-4) and 4.6 × 10(-4), respectively), and rs6001930 (MLK1) and rs17356907 (NTN4) with the absolute nondense volume (P = 6.7 × 10(-6) and 8.4 × 10(-5), respectively). Our results support the high heritability of mammographic density, though estimates are weaker for absolute than percent dense volume. We also demonstrate that the shared genetic component with breast cancer is not restricted to dense tissues only. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Heritability, assortative mating and gender differences in violent crime: results from a total population sample using twin, adoption, and sibling models.

PubMed

Frisell, Thomas; Pawitan, Yudi; Långström, Niklas; Lichtenstein, Paul

2012-01-01

Research addressing genetic and environmental determinants to antisocial behaviour suggests substantial variability across studies. Likewise, evidence for etiologic gender differences is mixed, and estimates might be biased due to assortative mating. We used longitudinal Swedish total population registers to estimate the heritability of objectively measured violent offending (convictions) in classic twin (N = 36,877 pairs), adoptee-parent (N = 5,068 pairs), adoptee-sibling (N = 10,610 pairs), and sibling designs (N = 1,521,066 pairs). Type and degree of assortative mating were calculated from comparisons between spouses of siblings and half-siblings, and across consecutive spouses. Heritability estimates for the liability of violent offending agreed with previously reported heritability for self-reported antisocial behaviour. While the sibling model yielded estimates similar to the twin model (A ≈ 55%, C ≈ 13%), adoptee-models appeared to underestimate familial effects (A ≈ 20-30%, C ≈ 0%). Assortative mating was moderate to strong (r (spouse) = 0.4), appeared to result from both phenotypic assortment and social homogamy, but had only minor effect on variance components. Finally, we found significant gender differences in the etiology of violent crime.

Heritability estimates of dental arch parameters in Lithuanian twins.

PubMed

Švalkauskienė, Vilma; Šmigelskas, Kastytis; Šalomskienė, Loreta; Andriuškevičiūtė, Irena; Šalomskienė, Aurelija; Vasiliauskas, Arūnas; Šidlauskas, Antanas

2015-01-01

The genetic influence on dental arch morphology may be country-specific, thus it is reasonable to check the estimates of genetics across different populations. The purpose of this study was to evaluate the heredity of dental arch morphology in the sample of Lithuanian twins with accurate zygosity determination. The study sample consisted of digital dental models of 40 monozygotic (MZ) and 32 dizygotic (DZ) twin pairs. The estimates of heritability (h(2)) for dental arch breadth and length were calculated. All dental arch breadths and lengths were statistically significantly larger in men than in women. Arch length differences between genders were less expressed than largest breadth differences. In the upper jaw the largest genetic effect was found on the arch breadth between lateral incisors. The heritability of dental arch length demonstrated similar differences between upper and lower jaw with mandible dental arch length being more genetically determined. The largest genetic impact was found on the upper dental arch breadth between lateral incisors. Similar, but lower heritability is inherent for canines and first premolars of the upper jaw and first premolars of the lower jaw. It also can be noted, that arch breadths between posterior teeth show lower heritability estimates than between anterior teeth on both jaws. The dental arch in the upper jaw has more expressed genetic component than in the lower jaw.

Heritability of the somatotype components in Biscay families.

PubMed

Rebato, E; Jelenkovic, A; Salces, I

2007-01-01

The anthropometric somatotype is a quantitative description of body shape and composition. Familial studies indicate the existence of a familial resemblance for this phenotype and they suggest a substantial action by genetic factors on this aggregation. The aim of this study is to examine the degree of familial resemblance of the somatotype components and of a factor of shape, in a sample of Biscay nuclear families (Basque Country, Spain). One thousand three hundred and thirty nuclear families were analysed. The anthropometric somatotype components [Carter, J.E.L., Heath, B.H., 1990. Somatotyping. Development and applications. Cambridge University Press, Cambridge, p. 503] were computed. Each component was fitted for the other two through a stepwise multiple regression, and also fitted through the LMS method [Cole, T., 1988. Fitting smoothed centile curves to reference data. J. Roy. Stat. Soc. 151, 385-418] in order to eliminate the age, sex and generation effects. The three raw components were introduced in a PCA from which a shape factor (PC1) was extracted for each generation. The correlations analysis was performed with the SEGPATH package [Province, M.A., Rao, D.C., 1995. General purpose model and computer programme for combined segregation and path analysis (SEGPATH): automatically creating computer from symbolic language model specifications. Genet. Epidemiol. 12, 203-219]. A general model of transmission and nine reduced models were tested. Maximal heritability was estimated with the formula of [Rice, T., Warwick, D.E., Gagnon, J., Bouchard, C., Leon, A.S., Skinner, J.S., Wilmore, J.H., Rao, D.C., 1997. Familial resemblance for body composition measures: the HERITAGE family study. Obes. Res. 5, 557-562]. The correlations were higher between offspring than in parents and offspring and a significant resemblance between mating partners existed. Maximum heritabilities were 55%, 52% and 46% for endomorphy, mesomorphy and ectomorphy, respectively, and 52% for PC1. In conclusion, the somatotype presents a moderate degree of familial aggregation. For the somatotype components, as well as for PC1, the degree of familial resemblance depends on age. The sex only has a significant effect on ectomorphy.

Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage.

PubMed

Prior, Steven J; Roth, Stephen M; Wang, Xiaojing; Kammerer, Candace; Miljkovic-Gacic, Iva; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

2007-10-01

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

PubMed Central

Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K.; Thomas, Venetta; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J.; Cheng, Iona; Chu, Lisa; Deming, Sandra L.; Driver, W. Ryan; Goodman, Phyllis; Hayes, Richard B.; Hennis, Anselm J. M.; Hsing, Ann W.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Kittles, Rick A.; Kolb, Suzanne; Leske, M. Cristina; Monroe, Kristine R.; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Ben A.; Schumacher, Fredrick; Stanford, Janet L.; Signorello, Lisa B.; Strom, Sara S.; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S.; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G.; Stram, Alexander H.; Kolonel, Laurence N.; Marchand, Loïc Le; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

2015-01-01

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious. PMID:26125186

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

PubMed

Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K; Thomas, Venetta; Ambrosone, Christine B; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J; Cheng, Iona; Chu, Lisa; Deming, Sandra L; Driver, W Ryan; Goodman, Phyllis; Hayes, Richard B; Hennis, Anselm J M; Hsing, Ann W; Hu, Jennifer J; Ingles, Sue A; John, Esther M; Kittles, Rick A; Kolb, Suzanne; Leske, M Cristina; Millikan, Robert C; Monroe, Kristine R; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Ben A; Schumacher, Fredrick; Stanford, Janet L; Signorello, Lisa B; Strom, Sara S; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G; Stram, Alexander H; Kolonel, Laurence N; Le Marchand, Loïc; Henderson, Brian E; Haiman, Christopher A; Stram, Daniel O

2015-01-01

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height.

PubMed

Fedko, Iryna O; Hottenga, Jouke-Jan; Medina-Gomez, Carolina; Pappa, Irene; van Beijsterveldt, Catharina E M; Ehli, Erik A; Davies, Gareth E; Rivadeneira, Fernando; Tiemeier, Henning; Swertz, Morris A; Middeldorp, Christel M; Bartels, Meike; Boomsma, Dorret I

2015-09-01

Combining genotype data across cohorts increases power to estimate the heritability due to common single nucleotide polymorphisms (SNPs), based on analyzing a Genetic Relationship Matrix (GRM). However, the combination of SNP data across multiple cohorts may lead to stratification, when for example, different genotyping platforms are used. In the current study, we address issues of combining SNP data from different cohorts, the Netherlands Twin Register (NTR) and the Generation R (GENR) study. Both cohorts include children of Northern European Dutch background (N = 3102 + 2826, respectively) who were genotyped on different platforms. We explore imputation and phasing as a tool and compare three GRM-building strategies, when data from two cohorts are (1) just combined, (2) pre-combined and cross-platform imputed and (3) cross-platform imputed and post-combined. We test these three strategies with data on childhood height for unrelated individuals (N = 3124, average age 6.7 years) to explore their effect on SNP-heritability estimates and compare results to those obtained from the independent studies. All combination strategies result in SNP-heritability estimates with a standard error smaller than those of the independent studies. We did not observe significant difference in estimates of SNP-heritability based on various cross-platform imputed GRMs. SNP-heritability of childhood height was on average estimated as 0.50 (SE = 0.10). Introducing cohort as a covariate resulted in ≈2 % drop. Principal components (PCs) adjustment resulted in SNP-heritability estimates of about 0.39 (SE = 0.11). Strikingly, we did not find significant difference between cross-platform imputed and combined GRMs. All estimates were significant regardless the use of PCs adjustment. Based on these analyses we conclude that imputation with a reference set helps to increase power to estimate SNP-heritability by combining cohorts of the same ethnicity genotyped on different platforms. However, important factors should be taken into account such as remaining cohort stratification after imputation and/or phenotypic heterogeneity between and within cohorts. Whether one should use imputation, or just combine the genotype data, depends on the number of overlapping SNPs in relation to the total number of genotyped SNPs for both cohorts, and their ability to tag all the genetic variance related to the specific trait of interest.

Accounting for Relatedness in Family Based Genetic Association Studies

PubMed Central

McArdle, P.F.; O’Connell, J.R.; Pollin, T.I.; Baumgarten, M.; Shuldiner, A.R.; Peyser, P.A.; Mitchell, B.D.

2007-01-01

Objective Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association. Methods We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families). Results Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11. Conclusion Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration. PMID:17570925

Heritability of Attractiveness to Mosquitoes

PubMed Central

Fernández-Grandon, G. Mandela; Gezan, Salvador A.; Armour, John A. L.; Pickett, John A.; Logan, James G.

2015-01-01

Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development. PMID:25901606

Cannabis dependence in the San Francisco Family Study: age of onset of use, DSM-IV symptoms, withdrawal, and heritability

PubMed Central

Ehlers, Cindy L.; Gizer, Ian R.; Vieten, Cassandra; Gilder, David A.; Stouffer, Gina M.; Lau, Philip; Wilhelmsen, Kirk C.

2009-01-01

Cannabis is the most widely used illicit drug in the United States, yet the role of genetics in individual symptoms associated with cannabis use disorders has not been evaluated. The purpose of the present set of analyses was to describe the symptomatology and estimate the heritability of DSM-IV criteria/symptoms of cannabis dependence in a large sample of families. Participants were 2524 adults, participating in the University of California San Francisco (UCSF) Family Study of alcoholism. Seventy percent of the sample had ever used cannabis and 13.9% met DSM-IV criteria for cannabis dependence. Younger age at first cannabis use was found to be significantly associated with a shortened survival to becoming cannabis dependent. Although a greater percentage of men met criteria for cannabis dependence, women were found to demonstrate “telescoping” as indexed by a shorter survival time from initial use to dependence as compared to men. A cannabis withdrawal syndrome was identified in users, the primary symptoms of which were nervousness, appetite change, and sleep disturbance. Cannabis use (h2 = 0.31) and dependence (h2 = 0.20), age at first use, individual DSM-IV criteria for dependence, and cannabis-use associated symptoms of depression, trouble concentrating and paranoia were all found to be heritable. These findings suggest that within this population that cannabis use and dependence, as well as individual cannabis dependence symptoms have a significant heritable component, that cannabis dependence is more likely to occur when use begins during adolescence, and that the cannabis dependence syndrome includes a number of heritable untoward psychiatric side effects including withdrawal. PMID:19818563

Genome-wide association identifies candidate genes for ovulation rate in swine

USDA-ARS?s Scientific Manuscript database

Litter size is an economically important trait to producers that is lowly heritable, observable only after considerable investment has been made in gilt development, and responds slowly to selection. Ovulation rate, a component trait of litter size, is moderately heritable, sex limited, and should r...

Nature or Nurture? Heritability in the Classroom.

PubMed

Hiramatsu, Layla; Garland, Theodore

Understanding evolution is a necessary component of undergraduate education in biology, and evolution is difficult to explain without studying the heritability of traits. However, in most classes, heritability is presented with only a handful of graphs showing typical morphological traits, for example, beak size in finches and height in humans. The active-inquiry exercise outlined in the following pages allows instructors to engage students in this formerly dry subject by bringing their own data as the basis for estimates of heritability. Students are challenged to come up with their own hypotheses regarding how and to what extent their traits are inherited from their parents and then gather, analyze data, and make inferences with help from the instructor. The exercise is simple in concept and execution but uncovers many new avenues of inquiry for students, including potential biases in their estimates of heritability and misconceptions that they may have had about the extent of inference that can be made from their heritability estimates. The active-inquiry format of the exercise prioritizes curiosity and discussion, leading to a much deeper understanding of heritability and the scientific method.

Heritability of articular cartilage regeneration and its association with ear wound healing in mice.

PubMed

Rai, Muhammad Farooq; Hashimoto, Shingo; Johnson, Eric E; Janiszak, Kara L; Fitzgerald, Jamie; Heber-Katz, Ellen; Cheverud, James M; Sandell, Linda J

2012-07-01

Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology, but little information is available on the genetics of cartilage regeneration. Therefore, this study was undertaken to investigate cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred (RI) lines generated from LG/J (healer of ear wounds) and SM/J (nonhealer) inbred mouse strains. An acute full-thickness cartilage injury was introduced in the trochlear groove of 8-week-old mice (n=265) through microsurgery. Mouse knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For the ear wound phenotype, a bilateral 2-mm through-and-through puncture was created in 6-week-old mice (n=229), and healing outcomes were measured after 30 days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Time-course analysis of the RI mouse lines showed no significant regeneration until 16 weeks after surgery; at that time, the strains could be segregated into 3 categories: good, intermediate, and poor healers. Analysis of heritability (H2) showed that both cartilage regeneration (H2=26%; P=0.006) and ear wound closure (H2=53%; P<0.00001) were significantly heritable. The genetic correlations between the two healing phenotypes for common inbred mouse strains (r=0.92) and RI mouse lines (r=0.86) were found to be extremely high. Our findings indicate that articular cartilage regeneration in mice is heritable, the differences between the mouse lines are due to genetic differences, and a strong genetic correlation between the two phenotypes exists, indicating that they plausibly share a common genetic basis. We therefore surmise that LG/J by SM/J intercross mice can be used to dissect the genetic basis of variation in cartilage regeneration. Copyright © 2012 by the American College of Rheumatology.

Nature vs nurture: are leaders born or made? A behavior genetic investigation of leadership style.

PubMed

Johnson, A M; Vernon, P A; McCarthy, J M; Molson, M; Harris, J A; Jang, K L

1998-12-01

With the recent resurgence in popularity of trait theories of leadership, it is timely to consider the genetic determination of the multiple factors comprising the leadership construct. Individual differences in personality traits have been found to be moderately to highly heritable, and so it follows that if there are reliable personality trait differences between leaders and non-leaders, then there may be a heritable component to these individual differences. Despite this connection between leadership and personality traits, however, there are no studies of the genetic basis of leadership using modern behavior genetic methodology. The present study proposes to address the lack of research in this area by examining the heritability of leadership style, as measured by self-report psychometric inventories. The Multifactor Leadership Questionnaire (MLQ), the Leadership Ability Evaluation, and the Adjective Checklist were completed by 247 adult twin pairs (183 monozygotic and 64 same-sex dizygotic). Results indicated that most of the leadership dimensions examined in this study are heritable, as are two higher level factors (resembling transactional and transformational leadership) derived from an obliquely rotated principal components factors analysis of the MLQ. Univariate analyses suggested that 48% of the variance in transactional leadership may be explained by additive heritability, and 59% of the variance in transformational leadership may be explained by non-additive (dominance) heritability. Multivariate analyses indicated that most of the variables studied shared substantial genetic covariance, suggesting a large overlap in the underlying genes responsible for the leadership dimensions.

Aggregate blood pressure responses to serial dietary sodium and potassium intervention: defining responses using independent component analysis.

PubMed

Chen, Gengsheng; de las Fuentes, Lisa; Gu, Chi C; He, Jiang; Gu, Dongfeng; Kelly, Tanika; Hixson, James; Jacquish, Cashell; Rao, D C; Rice, Treva K

2015-06-20

Hypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors. Aggregate indices such as principal components among these variables and their responses to environmental interventions may represent novel information that is potentially useful for genetic studies. In this study of families participating in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Study, blood pressure (BP) responses to dietary sodium interventions are explored. Independent component analysis (ICA) was applied to 20 variables indexing obesity and BP measured at baseline and during low sodium, high sodium and high sodium plus potassium dietary intervention periods. A "heat map" protocol that classifies subjects based on risk for hypertension is used to interpret the extracted components. ICA and heat map suggest four components best describe the data: (1) systolic hypertension, (2) general hypertension, (3) response to sodium intervention and (4) obesity. The largest heritabilities are for the systolic (64%) and general hypertension (56%) components. There is a pattern of higher heritability for the component response to intervention (40-42%) as compared to those for the traditional intervention responses computed as delta scores (24%-40%). In summary, the present study provides intermediate phenotypes that are heritable. Using these derived components may prove useful in gene discovery applications.

Heritability of lifetime ecstasy use.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vreeker, Annabel; Brunt, Tibor M; Willemsen, Gonneke; Boomsma, Dorret I; Vink, Jacqueline M

2017-09-01

Ecstasy is a widely used psychoactive drug that users often take because they experience positive effects such as increased euphoria, sociability, elevated mood, and heightened sensations. Ecstasy use is not harmless and several immediate and long term side effects have been identified. Lifetime ecstasy use is likely to be partly influenced by genetic factors, but no twin study has determined the heritability. Here, we apply a classical twin design to a large sample of twins and siblings to estimate the heritability of lifetime ecstasy use. The sample comprised 8500 twins and siblings aged between 18 and 45 years from 5402 families registered at the Netherlands Twin Registry. In 2013-2014 participants filled out a questionnaire including a question whether they had ever used ecstasy. We used the classical twin design to partition the individual differences in liability to ecstasy use into that due to genetic, shared environmental, and residual components. Overall, 10.4% of the sample had used ecstasy during their lifetime, with a somewhat higher prevalence in males than females. Twin modelling indicated that individual differences in liability to lifetime ecstasy use are for 74% due to genetic differences between individuals, whereas shared environmental and residual factors explain a small proportion of its liability (5% and 21%, respectively). Although heritability estimates appeared to be higher for females than males, this difference was not significant. Lifetime ecstasy use is a highly heritable trait, which indicates that some people are genetically more vulnerable to start using ecstasy than others. Copyright © 2017. Published by Elsevier B.V.

The low single nucleotide polymorphism heritability of plasma and saliva cortisol levels.

PubMed

Neumann, Alexander; Direk, Nese; Crawford, Andrew A; Mirza, Saira; Adams, Hieab; Bolton, Jennifer; Hayward, Caroline; Strachan, David P; Payne, Erin K; Smith, Jennifer A; Milaneschi, Yuri; Penninx, Brenda; Hottenga, Jouke J; de Geus, Eco; Oldehinkel, Albertine J; van der Most, Peter J; de Rijke, Yolanda; Walker, Brian R; Tiemeier, Henning

2017-11-01

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association Between Mortality and Heritability of the Scale of Aging Vigor in Epidemiology.

PubMed

Sanders, Jason L; Singh, Jatinder; Minster, Ryan L; Walston, Jeremy D; Matteini, Amy M; Christensen, Kaare; Mayeux, Richard; Borecki, Ingrid B; Perls, Thomas; Newman, Anne B

2016-08-01

To investigate the association between mortality and heritability of a rescaled Fried frailty index, the Scale of Aging Vigor in Epidemiology (SAVE), to determine its value for genetic analyses. Longitudinal, community-based cohort study. The Long Life Family Study (LLFS) in the United States and Denmark. Long-lived individuals (N = 4,875, including 4,075 genetically related individuals) and their families (N = 551). The SAVE was administered to 3,599 participants and included weight change, weakness (grip strength), fatigue (questionnaire), physical activity (days walked in prior 2 weeks), and slowness (gait speed); each component was scored 0, 1, or 2 using approximate tertiles, and summed (range 0 (vigorous) to 10 (frail)). Heritability was determined using a variance component-based family analysis using a polygenic model. Association with mortality in the proband generation (N = 1,421) was calculated using Cox proportional hazards mixed-effect models. Heritability of the SAVE was 0.23 (P < .001) overall (n = 3,599), 0.31 (P < .001) in probands (n = 1,479), and 0.26 (P < .001) in offspring (n = 2,120). In adjusted models, higher SAVE scores were associated with higher mortality (score 5-6: hazard ratio (HR) = 2.83, 95% confidence interval (CI) = 1.46-5.51; score 7-10: HR = 3.40, 95% CI = 1.72-6.71) than lower scores (0-2). The SAVE was associated with mortality and was moderately heritable in the LLFS, suggesting a genetic component to age-related vigor and frailty and supporting its use for further genetic analyses. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Heritability of brain activity related to response inhibition: A longitudinal genetic study in adolescent twins.

PubMed

Anokhin, Andrey P; Golosheykin, Simon; Grant, Julia D; Heath, Andrew C

2017-05-01

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

PubMed Central

Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

2017-01-01

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.

PubMed

Guo, W; Samuels, J F; Wang, Y; Cao, H; Ritter, M; Nestadt, P S; Krasnow, J; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Goes, F S; Maher, B; Pulver, A E; Valle, D; Mattheisen, M; Qian, J; Nestadt, G; Shugart, Y Y

2017-07-01

Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10 -7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data. Published by Elsevier B.V.

Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues.

PubMed

Wheeler, Heather E; Shah, Kaanan P; Brenner, Jonathon; Garcia, Tzintzuni; Aquino-Michaels, Keston; Cox, Nancy J; Nicolae, Dan L; Im, Hae Kyung

2016-11-01

Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR < 0.1) in the DGN whole blood cohort. However, current sample sizes (n ≤ 922) do not allow us to compute distal h2. Bayesian Sparse Linear Mixed Model (BSLMM) analysis provides strong evidence that the genetic contribution to local expression traits is dominated by a handful of genetic variants rather than by the collective contribution of a large number of variants each of modest size. In other words, the local architecture of gene expression traits is sparse rather than polygenic across all 40 tissues (from DGN and GTEx) examined. This result is confirmed by the sparsity of optimal performing gene expression predictors via elastic net modeling. To further explore the tissue context specificity, we decompose the expression traits into cross-tissue and tissue-specific components using a novel Orthogonal Tissue Decomposition (OTD) approach. Through a series of simulations we show that the cross-tissue and tissue-specific components are identifiable via OTD. Heritability and sparsity estimates of these derived expression phenotypes show similar characteristics to the original traits. Consistent properties relative to prior GTEx multi-tissue analysis results suggest that these traits reflect the expected biology. Finally, we apply this knowledge to develop prediction models of gene expression traits for all tissues. The prediction models, heritability, and prediction performance R2 for original and decomposed expression phenotypes are made publicly available (https://github.com/hakyimlab/PrediXcan).

Genetic Parameters and the Impact of Off-Types for Theobroma cacao L. in a Breeding Program in Brazil

PubMed Central

DuVal, Ashley; Gezan, Salvador A.; Mustiga, Guiliana; Stack, Conrad; Marelli, Jean-Philippe; Chaparro, José; Livingstone, Donald; Royaert, Stefan; Motamayor, Juan C.

2017-01-01

Breeding programs of cacao (Theobroma cacao L.) trees share the many challenges of breeding long-living perennial crops, and genetic progress is further constrained by both the limited understanding of the inheritance of complex traits and the prevalence of technical issues, such as mislabeled individuals (off-types). To better understand the genetic architecture of cacao, in this study, 13 years of phenotypic data collected from four progeny trials in Bahia, Brazil were analyzed jointly in a multisite analysis. Three separate analyses (multisite, single site with and without off-types) were performed to estimate genetic parameters from statistical models fitted on nine important agronomic traits (yield, seed index, pod index, % healthy pods, % pods infected with witches broom, % of pods other loss, vegetative brooms, diameter, and tree height). Genetic parameters were estimated along with variance components and heritabilities from the multisite analysis, and a trial was fingerprinted with low-density SNP markers to determine the impact of off-types on estimations. Heritabilities ranged from 0.37 to 0.64 for yield and its components and from 0.03 to 0.16 for disease resistance traits. A weighted index was used to make selections for clonal evaluation, and breeding values estimated for the parental selection and estimation of genetic gain. The impact of off-types to breeding progress in cacao was assessed for the first time. Even when present at <5% of the total population, off-types altered selections by 48%, and impacted heritability estimations for all nine of the traits analyzed, including a 41% difference in estimated heritability for yield. These results show that in a mixed model analysis, even a low level of pedigree error can significantly alter estimations of genetic parameters and selections in a breeding program. PMID:29250097

Ontogenetic variation of heritability and maternal effects in yellow-bellied marmot alarm calls.

PubMed

Blumstein, Daniel T; Nguyen, Kathy T; Martin, Julien G A

2013-05-07

Individuals of many species produce distinctive vocalizations that may relay potential information about the signaller. The alarm calls of some species have been reported to be individually specific, and this distinctiveness may allow individuals to access the reliability or kinship of callers. While not much is known generally about the heritability of mammalian vocalizations, if alarm calls were individually distinctive to permit kinship assessment, then call structure should be heritable. Here, we show conclusively for the first time that alarm call structure is heritable. We studied yellow-bellied marmots (Marmota flaviventris) and made nine quantitative measurements of their alarm calls. With a known genealogy, we used the animal model (a statistical technique) to estimate alarm call heritability. In juveniles, only one of the measured variables had heritability significantly different from zero; however, most variables had significant maternal environmental effects. By contrast, yearlings and adults had no significant maternal environmental effects, but the heritability of nearly all measured variables was significantly different from zero. Some, but not all of these heritable effects were significantly different across age classes. The presence of significantly non-zero maternal environmental effects in juveniles could reflect the impact of maternal environmental stresses on call structure. Regardless of this mechanism, maternal environmental effects could permit kinship recognition in juveniles. In older animals, the substantial genetic basis of alarm call structure suggests that calls could be used to assess kinship and, paradoxically, might also suggest a role of learning in call structure.

Ontogenetic variation of heritability and maternal effects in yellow-bellied marmot alarm calls

PubMed Central

Blumstein, Daniel T.; Nguyen, Kathy T.; Martin, Julien G. A.

2013-01-01

Individuals of many species produce distinctive vocalizations that may relay potential information about the signaller. The alarm calls of some species have been reported to be individually specific, and this distinctiveness may allow individuals to access the reliability or kinship of callers. While not much is known generally about the heritability of mammalian vocalizations, if alarm calls were individually distinctive to permit kinship assessment, then call structure should be heritable. Here, we show conclusively for the first time that alarm call structure is heritable. We studied yellow-bellied marmots (Marmota flaviventris) and made nine quantitative measurements of their alarm calls. With a known genealogy, we used the animal model (a statistical technique) to estimate alarm call heritability. In juveniles, only one of the measured variables had heritability significantly different from zero; however, most variables had significant maternal environmental effects. By contrast, yearlings and adults had no significant maternal environmental effects, but the heritability of nearly all measured variables was significantly different from zero. Some, but not all of these heritable effects were significantly different across age classes. The presence of significantly non-zero maternal environmental effects in juveniles could reflect the impact of maternal environmental stresses on call structure. Regardless of this mechanism, maternal environmental effects could permit kinship recognition in juveniles. In older animals, the substantial genetic basis of alarm call structure suggests that calls could be used to assess kinship and, paradoxically, might also suggest a role of learning in call structure. PMID:23466987

Dissection of two QTL on SSC2 identifies candidate genes for ovulation rate in swine

USDA-ARS?s Scientific Manuscript database

Litter size is an economically important trait to producers that is lowly heritable, observable only after considerable investment has been made in gilt development and responds slowly to selection. Ovulation rate, a component trait of litter size, is moderately heritable, sex limited and should res...

Genetic Divergence and Heritability of 42 Coloured Upland Rice Genotypes (Oryzasativa) as Revealed by Microsatellites Marker and Agro-Morphological Traits

PubMed Central

Ahmad, Faiz; Hanafi, Mohamed Musa; Hakim, Md Abdul; Rafii, Mohd Y.; Arolu, Ibrahim Wasiu; Akmar Abdullah, Siti Nor

2015-01-01

Coloured rice genotypes have greater nutritious value and consumer demand for these varieties is now greater than ever. The documentation of these genotypes is important for the improvement of the rice plant. In this study, 42 coloured rice genotypes were selected for determination of their genetic divergence using 25 simple sequence repeat (SSR) primers and 15 agro-morphological traits. Twenty-one out of the 25 SSR primers showed distinct, reproducible polymorphism. A dendrogram constructed using the SSR primers clustered the 42 coloured rice genotypes into 7 groups. Further, principle component analysis showed 75.28% of total variations were explained by the first—three components. All agro-morphological traits showed significant difference at the (p≤0.05) and (p≤0.01) levels. From the dendrogram constructed using the agro-morphological traits, all the genotypes were clustered into four distinct groups. Pearson’s correlation coefficient showed that among the 15 agro-morphological traits, the yield contributing factor had positive correlation with the number of tillers, number of panicles, and panicle length. The heritability of the 15 traits ranged from 17.68 to 99.69%. Yield per plant and harvest index showed the highest value for both heritability and genetic advance. The information on the molecular and agro-morphological traits can be used in rice breeding programmes to improve nutritional value and produce higher yields. PMID:26393807

Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

PubMed

Musani, Solomon K; Martin, Lisa J; Woo, Jessica G; Olivier, Michael; Gurka, Matthew J; DeBoer, Mark D

2017-04-01

Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences. © 2017 American Heart Association, Inc.

Genetics of wellbeing and its components satisfaction with life, happiness, and quality of life: a review and meta-analysis of heritability studies.

PubMed

Bartels, Meike

2015-03-01

Wellbeing is a major topic of research across several disciplines, reflecting the increasing recognition of its strong value across major domains in life. Previous twin-family studies have revealed that individual differences in wellbeing are accounted for by both genetic as well as environmental factors. A systematic literature search identified 30 twin-family studies on wellbeing or a related measure such as satisfaction with life or happiness. Review of these studies showed considerable variation in heritability estimates (ranging from 0 to 64 %), which makes it difficult to draw firm conclusions regarding the genetic influences on wellbeing. For overall wellbeing twelve heritability estimates, from 10 independent studies, were meta-analyzed by computing a sample size weighted average heritability. Ten heritability estimates, derived from 9 independent samples, were used for the meta-analysis of satisfaction with life. The weighted average heritability of wellbeing, based on a sample size of 55,974 individuals, was 36 % (34-38), while the weighted average heritability for satisfaction with life was 32 % (29-35) (n = 47,750). With this result a more robust estimate of the relative influence of genetic effects on wellbeing is provided.

Quantitative genetics of human morphology and obesity-related phenotypes in nuclear families from the Greater Bilbao (Spain): comparison with other populations.

PubMed

Jelenkovic, Aline; Poveda, Alaitz; Rebato, Esther

2011-07-01

It is well established that variation of soft-tissue traits is less influenced by the genetic component than skeletal traits. However, it is still unclear whether heritabilities (h(2)) of obesity-related phenotypes present a common pattern across populations. To estimate familial resemblance and heritability of body size, shape and composition phenotypes and to compare these results with those from other populations. The subject group consisted of 533 nuclear families living in Greater Bilbao and included 1702 individuals aged 2-61 years. Familial correlations and h(2) were estimated for 29 anthropometric phenotypes (19 simple measures, three derived factors, four obesity indices and the three Heath-Carter somatotype components) using MAN and SOLAR programmes. All phenotypes were influenced by additive genetic factors with narrow sense heritabilities ranging from 0.28-0.69. In general, skeletal traits exhibited the highest h(2), whereas phenotypes defining the amount of adipose tissue, particularly central fat, were less determined by genetic factors. Familial correlations and heritability estimates of body morphology and composition from the Greater Bilbao sample were within the range observed in other studies. The lower heritability detected for central fat has also been found in some other populations, but further investigations in different populations using the same anthropometric traits and estimation methods are needed in order to obtain more robust conclusions.

Association with Mortality and Heritability of the Scale of Aging Vigor in Epidemiology (SAVE)

PubMed Central

Sanders, Jason L.; Singh, Jatinder; Minster, Ryan L.; Walston, Jeremy D.; Matteini, Amy M.; Christensen, Kaare; Mayeux, Richard; Borecki, Ingrid B.; Perls, Thomas; Newman, Anne B.

2016-01-01

Background Vigor may be an important phenotype of healthy aging. Factors that prevent frailty or conversely promote vigor are of interest. Using the Long Life Family Study (LLFS), we investigated the association with mortality and heritability of a rescaled Fried frailty index, the Scale of Aging Vigor in Epidemiology (SAVE), to determine its value for genetic analyses. Design/Setting Longitudinal, community-based cohort study of long lived individuals and their families (N=4075 genetically-related individuals) in the United States and Denmark. Methods The SAVE was measured in 3599 participants and included weight change, weakness (grip strength), fatigue (questionnaire), physical activity (days walked in prior 2 weeks), and slowness (gait speed), each component scored 0, 1 or 2 using approximate tertiles, and summed from 0 (vigorous) to 10 (frail). Heritability was determined with a variance-component based family analysis using a polygenic model. Association with mortality in the proband generation (N=1421) was calculated with Cox proportional hazards mixed effect models. Results Heritability of the SAVE was 0.23 (p = 1.72 × 10−13) overall (n=3599), 0.31 (p = 2.00 × 10−7) in probands (n=1479), and 0.26 (p = 2.00 × 10−6) in offspring (n=2120). In adjusted models, compared with lower SAVE scores (0–2), higher scores were associated with higher mortality (score 5–6 HR, 95%CI = 2.83, 1.46–5.51; score 7–10 HR, 95% CI = 3.40, 1.72–6.71). Conclusion The SAVE was associated with mortality and was moderately heritable in the LLFS, suggesting a genetic component to age-related vigor and frailty and supporting its use for further genetic analyses. PMID:27294813

Genome‐wide association study of facial emotion recognition in children and association with polygenic risk for mental health disorders

PubMed Central

Coleman, Jonathan R.I.; Lester, Kathryn J.; Keers, Robert; Munafò, Marcus R.; Breen, Gerome

2017-01-01

Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight‐year‐old participants (n = 4,097) from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Diagnostic Analysis of Non‐Verbal Accuracy (DANVA) faces test. Genome‐wide genotype data was available from the Illumina HumanHap550 Quad microarray. Genome‐wide association studies were performed to assess associations with recognition of individual emotions and emotion in general. Exploratory polygenic risk scoring was performed using published genomic data for schizophrenia, bipolar disorder, depression, autism spectrum disorder, anorexia, and anxiety disorders. No individual genetic variants were identified at conventional levels of significance in any analysis although several loci were associated at a level suggestive of significance. SNP‐chip heritability analyses did not identify a heritable component of variance for any phenotype. Polygenic scores were not associated with any phenotype. The effect sizes of variants influencing emotion recognition are likely to be small. Previous studies of emotion identification have yielded non‐zero estimates of SNP‐heritability. This discrepancy is likely due to differences in the measurement and analysis of the phenotype. PMID:28608620

A General Definition of the Heritable Variation That Determines the Potential of a Population to Respond to Selection

PubMed Central

Bijma, Piter

2011-01-01

Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population’s intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes the concept of heritable variance to any inheritance model and level of organization. The result shows that heritable variance determining potential response to selection is the variance among individuals in the heritable quantity that determines the population mean trait value, rather than the usual additive genetic component of phenotypic variance. It follows, therefore, that heritable variance may exceed phenotypic variance among individuals, which is impossible in classical theory. This work also provides a measure of the utilization of heritable variation for response to selection and integrates two well-known models of maternal genetic effects. The result shows that relatedness between the focal individual and the individuals affecting its fitness is a key determinant of the utilization of heritable variance for response to selection. PMID:21926298

A general definition of the heritable variation that determines the potential of a population to respond to selection.

PubMed

Bijma, Piter

2011-12-01

Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population's intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes the concept of heritable variance to any inheritance model and level of organization. The result shows that heritable variance determining potential response to selection is the variance among individuals in the heritable quantity that determines the population mean trait value, rather than the usual additive genetic component of phenotypic variance. It follows, therefore, that heritable variance may exceed phenotypic variance among individuals, which is impossible in classical theory. This work also provides a measure of the utilization of heritable variation for response to selection and integrates two well-known models of maternal genetic effects. The result shows that relatedness between the focal individual and the individuals affecting its fitness is a key determinant of the utilization of heritable variance for response to selection.

Inheritance of Vertebral Number in the Three-Spined Stickleback (Gasterosteus aculeatus)

PubMed Central

Alho, Jussi S.; Leinonen, Tuomas; Merilä, Juha

2011-01-01

Intraspecific variation in the number of vertebrae is taxonomically widespread, and both genetic and environmental factors are known to contribute to this variation. However, the relative importance of genetic versus environmental influences on variation in vertebral number has seldom been investigated with study designs that minimize bias due to non-additive genetic and maternal influences. We used a paternal half-sib design and animal model analysis to estimate heritability and causal components of variance in vertebral number in three-spined sticklebacks (Gasterosteus aculeatus). We found that both the number of vertebrae (h2 = 0.36) and body size (h2 = 0.42) were moderately heritable, whereas the influence of maternal effects was estimated to be negligible. While the number of vertebrae had a positive effect on body size, no evidence for a genetic correlation between body size and vertebral number was detected. However, there was a significant positive environmental correlation between these two traits. Our results support the generalization-in accordance with results from a review of heritability estimates for vertebral number in fish, reptiles and mammals-that the number of vertebrae appears to be moderately to highly heritable in a wide array of species. In the case of the three-spined stickleback, independent evolution of body size and number of vertebrae should be possible given the low genetic correlation between the two traits. PMID:21603609

A sibling based design to quantify genetic and shared environmental effects of venous thromboembolism in Sweden.

PubMed

Zöller, Bengt; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2017-01-01

Few large studies have examined the heritability of venous thromboembolism (VTE). Moreover, twin studies have been suggested to overestimate heritability. The aim of the present study was to determine the heritability nationwide in the general Swedish population using full siblings and half-siblings. VTE was defined using the Swedish patient register. Full sibling (FS) and half-sibling (HS) pairs born 1950-1990 were obtained from the Swedish Multi-generation Register. A maximum of 5years age difference was allowed. We also required that the individuals within the pair should reside in the same household for at least 8years or not at all (0years) before the youngest turned 16. Information about sibling pair residence within the same household, small residential area, and municipality was obtained from Statistics Sweden. We assumed three potential sources of liability to VTE: additive genetic (A), shared (or common/familial) environment (C), and unique environment (E) components. Totally 881,206 FS pairs and 95,198 HS pairs were included. The full model predicted heritability for VTE with 47% for males and 40% for females. Environmental factors shared by siblings contributed to 0% of the variance in liability for both sexes, and unique environment (E) components accounted for 53% in males and 60% in females. The high heritability of VTE risk indicates that genetic susceptibility plays a substantial role for VTE in the Swedish general population. Overestimation of heritability from twin studies is not likely. The proportion of the variance attributable to shared familial environment factors is small. Subject codes: Genetics, epidemiology, thrombosis, cardiovascular disease, embolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Whole genome prediction and heritability of childhood asthma phenotypes.

PubMed

McGeachie, Michael J; Clemmer, George L; Croteau-Chonka, Damien C; Castaldi, Peter J; Cho, Michael H; Sordillo, Joanne E; Lasky-Su, Jessica A; Raby, Benjamin A; Tantisira, Kelan G; Weiss, Scott T

2016-12-01

While whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma-related phenotypes. We applied several WGP methods to a well-phenotyped cohort of 832 children with mild-to-moderate asthma from CAMP. We assessed narrow-sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre- and post-bronchodilator forced expiratory volume in 1 sec (FEV 1 ), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort. We found that longitudinal lung function phenotypes demonstrated significant narrow-sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4-8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts. Longitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP-prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma-related heritable traits.

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

PubMed Central

Light, Gregory; Greenwood, Tiffany A.; Swerdlow, Neal R.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Background: Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes. Methods: Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. Results: The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Conclusions: Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. PMID:24903414

Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study.

PubMed

Light, Gregory; Greenwood, Tiffany A; Swerdlow, Neal R; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2014-11-01

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a "heritability gap" between the diagnosis and related endophenotypes. Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2014.

Genetic and environmental influences on Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) maladaptive personality traits and their connections with normative personality traits.

PubMed

Wright, Zara E; Pahlen, Shandell; Krueger, Robert F

2017-05-01

The Diagnostic and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5) proposes an alternative model for personality disorders, which includes maladaptive-level personality traits. These traits can be operationalized by the Personality Inventory for the DSM-5 (PID-5). Although there has been extensive research on genetic and environmental influences on normative level personality, the heritability of the DSM-5 traits remains understudied. The present study addresses this gap in the literature by assessing traits indexed by the PID-5 and the International Personality Item Pool NEO (IPIP-NEO) in adult twins (N = 1,812 individuals). Research aims include (a) replicating past findings of the heritability of normative level personality as measured by the IPIP-NEO as a benchmark for studying maladaptive level traits, (b) ascertaining univariate heritability estimates of maladaptive level traits as measured by the PID-5, (c) establishing how much variation in personality pathology can be attributed to the same genetic components affecting variation in normative level personality, and (d) determining residual variance in personality pathology domains after variance attributable to genetic and environmental components of general personality has been removed. Results revealed that PID-5 traits reflect similar levels of heritability to that of IPIP-NEO traits. Further, maladaptive and normative level traits that correlate at the phenotypic level also correlate at the genotypic level, indicating overlapping genetic components contribute to variance in both. Nevertheless, we also found evidence for genetic and environmental components unique to maladaptive level personality traits, not shared with normative level traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

PubMed

Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R

2015-08-01

The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.

Quantitative trait locus mapping and analysis of heritable variation in affiliative social behavior and co-occurring traits.

PubMed

Knoll, A T; Jiang, K; Levitt, P

2018-06-01

Humans exhibit broad heterogeneity in affiliative social behavior. Twin and family studies show that individual differences in core dimensions of social behavior are heritable, yet there are knowledge gaps in understanding the underlying genetic and neurobiological mechanisms. Animal genetic reference panels (GRPs) provide a tractable strategy for examining the behavioral and genetic architecture of complex traits. Here, using males from 50 mouse strains from the BXD GRP, 4 domains of affiliative social behavior-social approach, social recognition, direct social interaction (DSI) (partner sniffing) and vocal communication-were examined in 2 widely used behavioral tasks-the 3-chamber and DSI tasks. There was continuous and broad variation in social and nonsocial traits, with moderate to high heritability of social approach sniff preference (0.31), ultrasonic vocalization (USV) count (0.39), partner sniffing (0.51), locomotor activity (0.54-0.66) and anxiety-like behavior (0.36). Principal component analysis shows that variation in social and nonsocial traits are attributable to 5 independent factors. Genome-wide mapping identified significant quantitative trait loci for USV count on chromosome (Chr) 18 and locomotor activity on Chr X, with suggestive loci and candidate quantitative trait genes identified for all traits with one notable exception-partner sniffing in the DSI task. The results show heritable variation in sociability, which is independent of variation in activity and anxiety-like traits. In addition, a highly heritable and ethological domain of affiliative sociability-partner sniffing-appears highly polygenic. These findings establish a basis for identifying functional natural variants, leading to a new understanding typical and atypical sociability. © 2017 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

Repeatability and Heritability of Behavioural Types in a Social Cichlid

PubMed Central

Chervet, Noémie; Zöttl, Markus; Schürch, Roger; Taborsky, Michael; Heg, Dik

2011-01-01

Aim. The quantitative genetics underlying correlated behavioural traits (‘‘animal personality”) have hitherto been studied mainly in domesticated animals. Here we report the repeatability (R) and heritability (h2) of behavioural types in the highly social cichlid fish Neolamprologus pulcher. Methods. We tested 1779 individuals repeatedly and calculated the h2 of behavioural types by variance components estimation (GLMM REML), using 1327 offspring from 162 broods from 74 pairs. Results. Repeatability of behavioural types was significant and considerable (0.546), but declined from 0.83 between tests conducted on the same day, to 0.19 on tests conducted up to 1201 days apart. All h2 estimates were significant but low (e.g., pair identity h2 = 0.15 ± 0.03 SE). Additionally, we found significant variation between broods nested within the parent(s), but these were not related to several environmental factors tested. Conclusions. We conclude that despite a considerable R, h2 in this cichlid species is low, and variability in behavioural type appears to be strongly affected by other (non)genetic effects. PMID:21716729

Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

PubMed

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-03-09

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

PubMed Central

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-01-01

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

Inheritance of Occlusal Topography: A Twin Study

PubMed Central

Su, C-Y.; Corby, P.M.; Elliot, M.A.; Studen-Pavlovich, D.A.; Ranalli, D.N.; Rosa, B.; Wessel, J.; Schork, N.J.; Hart, T.C.; Bretz, W.A.

2011-01-01

Aim This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. Methods The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. Results DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. Conclusions Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars. PMID:18328234

Sex-specific genetic variances in life-history and morphological traits of the seed beetle Callosobruchus maculatus.

PubMed

Hallsson, Lára R; Björklund, Mats

2012-01-01

Knowledge of heritability and genetic correlations are of central importance in the study of adaptive trait evolution and genetic constraints. We use a paternal half-sib-full-sib breeding design to investigate the genetic architecture of three life-history and morphological traits in the seed beetle, Callosobruchus maculatus. Heritability was significant for all traits under observation and genetic correlations between traits (r(A)) were low. Interestingly, we found substantial sex-specific genetic effects and low genetic correlations between sexes (r(MF)) in traits that are only moderately (weight at emergence) to slightly (longevity) sexually dimorphic. Furthermore, we found an increased sire ([Formula: see text]) compared to dam ([Formula: see text]) variance component within trait and sex. Our results highlight that the genetic architecture even of the same trait should not be assumed to be the same for males and females. Furthermore, it raises the issue of the presence of unnoticed environmental effects that may inflate estimates of heritability. Overall, our study stresses the fact that estimates of quantitative genetic parameters are not only population, time, environment, but also sex specific. Thus, extrapolation between sexes and studies should be treated with caution.

Sex-specific genetic variances in life-history and morphological traits of the seed beetle Callosobruchus maculatus

PubMed Central

Hallsson, Lára R; Björklund, Mats

2012-01-01

Knowledge of heritability and genetic correlations are of central importance in the study of adaptive trait evolution and genetic constraints. We use a paternal half-sib-full-sib breeding design to investigate the genetic architecture of three life-history and morphological traits in the seed beetle, Callosobruchus maculatus. Heritability was significant for all traits under observation and genetic correlations between traits (rA) were low. Interestingly, we found substantial sex-specific genetic effects and low genetic correlations between sexes (rMF) in traits that are only moderately (weight at emergence) to slightly (longevity) sexually dimorphic. Furthermore, we found an increased sire () compared to dam () variance component within trait and sex. Our results highlight that the genetic architecture even of the same trait should not be assumed to be the same for males and females. Furthermore, it raises the issue of the presence of unnoticed environmental effects that may inflate estimates of heritability. Overall, our study stresses the fact that estimates of quantitative genetic parameters are not only population, time, environment, but also sex specific. Thus, extrapolation between sexes and studies should be treated with caution. PMID:22408731

Lessons on the pathogenesis of aneurysm from heritable conditions

PubMed Central

Lindsay, Mark E.; Dietz, Harry C.

2013-01-01

Aortic aneurysm is common, accounting for 1–2% of all deaths in industrialized countries. Early theories of the causes of human aneurysm mostly focused on inherited or acquired defects in components of the extracellular matrix in the aorta. Although several mutations in the genes encoding extracellular matrix proteins have been recognized, more recent discoveries have shown important perturbations in cytokine signalling cascades and intracellular components of the smooth muscle contractile apparatus. The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-β cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies. PMID:21593863

Heritability of lenticular myopia in English Springer spaniels.

PubMed

Kubai, Melissa A; Labelle, Amber L; Hamor, Ralph E; Mutti, Donald O; Famula, Thomas R; Murphy, Christopher J

2013-11-08

We determined whether naturally-occurring lenticular myopia in English Springer spaniels (ESS) has a genetic component. Streak retinoscopy was performed on 226 related ESS 30 minutes after the onset of pharmacologic mydriasis and cycloplegia. A pedigree was constructed to determine relationships between affected offspring and parents. Estimation of heritability was done in a Bayesian analysis (facilitated by the MCMCglmm package of R) of refractive error in a model, including terms for sex and coat color. Myopia was defined as ≤-0.5 diopters (D) spherical equivalent. The median refractive error for ESS was 0.25 D (range, -3.5 to +4.5 D). Median age was 0.2 years (range, 0.1-15 years). The prevalence of myopia in related ESS was 19% (42/226). The ESS had a strong correlation (r = 0.95) for refractive error between the two eyes. Moderate heritability was present for refractive error with a mean value of 0.29 (95% highest probability density, 0.07-0.50). The distribution of refractive error, and subsequently lenticular myopia, has a moderate genetic component in ESS. Further investigation of genes responsible for regulation of the development of refractive ocular components in canines is warranted.

Comparing estimates of genetic variance across different relationship models.

PubMed

Legarra, Andres

2016-02-01

Use of relationships between individuals to estimate genetic variances and heritabilities via mixed models is standard practice in human, plant and livestock genetics. Different models or information for relationships may give different estimates of genetic variances. However, comparing these estimates across different relationship models is not straightforward as the implied base populations differ between relationship models. In this work, I present a method to compare estimates of variance components across different relationship models. I suggest referring genetic variances obtained using different relationship models to the same reference population, usually a set of individuals in the population. Expected genetic variance of this population is the estimated variance component from the mixed model times a statistic, Dk, which is the average self-relationship minus the average (self- and across-) relationship. For most typical models of relationships, Dk is close to 1. However, this is not true for very deep pedigrees, for identity-by-state relationships, or for non-parametric kernels, which tend to overestimate the genetic variance and the heritability. Using mice data, I show that heritabilities from identity-by-state and kernel-based relationships are overestimated. Weighting these estimates by Dk scales them to a base comparable to genomic or pedigree relationships, avoiding wrong comparisons, for instance, "missing heritabilities". Copyright © 2015 Elsevier Inc. All rights reserved.

Body condition score of Nellore beef cows: a heritable measure to improve the selection of reproductive and maternal traits.

PubMed

Fernandes, A F A; Neves, H H R; Carvalheiro, R; Oliveira, J A; Queiroz, S A

2015-08-01

Despite the economic importance of beef cattle production in Brazil, female reproductive performance, which is strongly associated with production efficiency, is not included in the selection index of most breeding programmes due to low heritability and difficulty in measure. The body condition score (BCS) could be used as an indicator of these traits. However, so far little is known about the feasibility of using BCS as a selection tool for reproductive performance in beef cattle. In this study, we investigated the sources of variation in the BCS of Nellore beef cows, quantified its association with reproductive and maternal traits and estimated its heritability. BCS was analysed using a logistic model that included the following effects: contemporary group at weaning, cow weight and hip height, calving order, reconception together with the weight and scores of conformation and early finishing assigned to calves at weaning. In the genetic analysis, variance components of BCS were estimated through Bayesian inference by fitting an animal model that also included the aforementioned effects. The results showed that BCS was significantly associated with all of the reproductive and maternal variables analysed. The estimated posterior mean of heritability of BCS was 0.24 (highest posterior density interval at 95%: 0.093 to 0.385), indicating an involvement of additive gene action in its determination. The present findings show that BCS can be used as a selection criterion for Nellore females.

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

PubMed

Yang, Qiong; Tofler, Geoffrey H; Cupples, L Adrienne; Larson, Martin G; Feng, DaLi; Lindpaintner, Klaus; Levy, Daniel; D'Agostino, Ralph B; O'Donnell, Christopher J

2003-04-15

Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

The genetics of human obesity.

PubMed

Xia, Qianghua; Grant, Struan F A

2013-04-01

It has long been known that there is a genetic component to obesity, and that characterizing this underlying factor would likely offer the possibility of better intervention in the future. Monogenic obesity has proved to be relatively straightforward, with a combination of linkage analysis and mouse models facilitating the identification of multiple genes. In contrast, genome-wide association studies have successfully revealed a variety of genetic loci associated with the more common form of obesity, allowing for very strong consensus on the underlying genetic architecture of the phenotype for the first time. Although a number of significant findings have been made, it appears that very little of the apparent heritability of body mass index has actually been explained to date. New approaches for data analyses and advances in technology will be required to uncover the elusive missing heritability, and to aid in the identification of the key causative genetic underpinnings of obesity. © 2013 New York Academy of Sciences.

Higher heritabilities for gait components than for overall gait scores may improve mobility in ducks.

PubMed

Duggan, Brendan M; Rae, Anne M; Clements, Dylan N; Hocking, Paul M

2017-05-02

Genetic progress in selection for greater body mass and meat yield in poultry has been associated with an increase in gait problems which are detrimental to productivity and welfare. The incidence of suboptimal gait in breeding flocks is controlled through the use of a visual gait score, which is a subjective assessment of walking ability of each bird. The subjective nature of the visual gait score has led to concerns over its effectiveness in reducing the incidence of suboptimal gait in poultry through breeding. The aims of this study were to assess the reliability of the current visual gait scoring system in ducks and to develop a more objective method to select for better gait. Experienced gait scorers assessed short video clips of walking ducks to estimate the reliability of the current visual gait scoring system. Kendall's coefficients of concordance between and within observers were estimated at 0.49 and 0.75, respectively. In order to develop a more objective scoring system, gait components were visually scored on more than 4000 pedigreed Pekin ducks and genetic parameters were estimated for these components. Gait components, which are a more objective measure, had heritabilities that were as good as, or better than, those of the overall visual gait score. Measurement of gait components is simpler and therefore more objective than the standard visual gait score. The recording of gait components can potentially be automated, which may increase accuracy further and may improve heritability estimates. Genetic correlations were generally low, which suggests that it is possible to use gait components to select for an overall improvement in both economic traits and gait as part of a balanced breeding programme.

Chemotherapy induced toxicity is highly heritable in Drosophila melanogaster

PubMed Central

Kislukhin, Galina; Murphy, Maura L.; Jafari, Mahtab; Long, Anthony D.

2012-01-01

Objectives Identifying the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. In order to develop Drosophila melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high throughput toxicity assays and prove that inter-individual variation in toxicity as measured by such assays is highly heritable. Methods We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed via a decrease in female fecundity. Chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride. Results We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose dependent and highly heritable manner. The following heritability estimates were found: carboplatin – 0.72, floxuridine – 0.52, gemcitabine hydrochloride – 0.72, methotrexate – 0.99, mitomycin C – 0.64, and topotecan hydrochloride – 0.63. Conclusions The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component. PMID:22336958

Genetic Risk Variants for Social Anxiety

PubMed Central

Stein, Murray B.; Chen, Chia-Yen; Jain, Sonia; Jensen, Kevin P.; He, Feng; Heeringa, Steven G.; Kessler, Ronald C.; Maihofer, Adam; Nock, Matthew K.; Ripke, Stephan; Sun, Xiaoying; Thomas, Michael L.; Ursano, Robert J.; Smoller, Jordan W.; Gelernter, Joel

2017-01-01

Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Service members (Army STARRS) to (1) determine SNP-based heritability of social anxiety; (2) discern genetic risk loci for social anxiety; and (3) determine shared genetic risk with neuroticism and extraversion. GWAS were conducted within ancestral groups (EUR, AFR, LAT) using linear regression models for each of the 3 component studies in Army STARRS, and then meta-analyzed across studies. SNP-based heritability for social anxiety was significant (h2g=0.12, p=2.17×10-4 in EUR). One meta-analytically genomewide significant locus was seen in each of EUR (rs708012, Chr 6: BP 36965970, p = 1.55×10-8; beta = 0.073) and AFR (rs78924501, Chr 1: BP 88406905, p = 3.58×10-8; beta = 0.265) samples. Social anxiety in Army STARRS was significantly genetically correlated (negatively) with extraversion (rg = -0.52, se = 0.22, p = 0.02) but not with neuroticism (rg = 0.05, se = 0.22, p = 0.81) or with an anxiety disorder factor score (rg = 0.02, se = 0.32, p = 0.94) from external GWAS meta-analyses. This first GWAS of social anxiety confirms a genetic basis for social anxiety, shared with extraversion but possibly less so with neuroticism. PMID:28224735

Micrometric Control of the Optics of the Human Eye: Environment or Genes?

PubMed

Tabernero, Juan; Hervella, Lucía; Benito, Antonio; Colodro-Conde, Lucía; Ordoñana, Juan R; Ruiz-Sanchez, Marcos; Marín, José María; Artal, Pablo

2017-04-01

The human eye has typically more optical aberrations than conventional artificial optical systems. While the lower order modes (defocus and astigmatism) are well studied, our purpose is to explore the influence of genes versus the environment on the higher order aberrations of the optical components of the eye. We have performed a classical twin study in a sample from the Region of Murcia (Spain). Optical aberrations using a Hartmann-Shack sensor (AOnEye Voptica SL, Murcia, Spain) and corneal aberrations (using corneal topography data) were measured in 138 eyes corresponding to 69 twins; 36 monozygotic (MZ) and 33 dizygotic (DZ) pairs (age 55 years, SD 7 years). Intraclass correlation coefficients (ICCs) were used to estimate how strongly aberrations of twins resemble each other, and genetic models were fitted to quantify heritability in the selected phenotypes. Genes had a significant influence in the variance of most of the higher order aberration terms (heritability from 40% to 70%). This genetic influence was observed similarly in both cornea and complete eye aberrations. Additionally, the compensation factor of spherical aberration in the eye (i.e., how much corneal spherical aberration was compensated by internal spherical aberration) was found under genetic influence (heritability of 68%). There is a significant genetic contribution to the variance of aberrations of the eye, not only at macroscopic levels, as in myopia or astigmatism, but also at microscopic levels, where a few micrometers changes in surface topography can produce a large difference in the value of the optical aberrations.

An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2.

PubMed

Kim, Jaemin; Lee, Taeheon; Kim, Tae-Hun; Lee, Kyung-Tai; Kim, Heebal

2012-12-19

Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa), may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05) and type 2 diabetes (P = 0.00578). Through the estimation of variance of genetic component (heritability) for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479) between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15) was most important in explaining the phenotypic variance for obesity. Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B.

Heritability of vaccine-induced measles neutralizing antibody titers.

PubMed

Schaid, Daniel J; Haralambieva, Iana H; Larrabee, Beth R; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

2017-03-07

Understanding how genetics influences inter-individual variation of antibody titers in response to measles vaccination is vital to understanding possible sources of vaccine failure as well as improved vaccine development. Although it is recognized that both the human leukocyte antigen (HLA) genes and the immunoglobulin allotype genes play significant roles in immune response, there is significant variation in antibody titers that is not explained by these genes. To obtain a more complete estimate of the role of the entire genome, we used a large panel of single nucleotide polymorphisms to estimate the heritability of antibody response to measles vaccine. Based on 935 subjects with European ancestry, we estimated the heritability to be 49% (standard error 0.17). We also estimated the heritability attributable to each chromosome, and found a large range in chromosome-specific heritabilities. Notably, chromosome 1 had the largest estimate (28%), while chromosome 6, which harbors HLA, had an estimated heritability of 13%. Compared with a prior study of twins in the same community, which resulted in a heritability estimate of 88.5%, our study suggests there are either many rare genetic variants, or many common genetic variants of small effect sizes that contribute to variations of antibody titers in response to measles vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genes influence young children's human figure drawings and their association with intelligence a decade later.

PubMed

Arden, Rosalind; Trzaskowski, Maciej; Garfield, Victoria; Plomin, Robert

2014-10-01

Drawing is ancient; it is the only childhood cognitive behavior for which there is any direct evidence from the Upper Paleolithic. Do genes influence individual differences in this species-typical behavior, and is drawing related to intelligence (g) in modern children? We report on the first genetically informative study of children's figure drawing. In a study of 7,752 pairs of twins, we found that genetic differences exert a greater influence on children's figure drawing at age 4 than do between-family environmental differences. Figure drawing was as heritable as g at age 4 (heritability of .29 for both). Drawing scores at age 4 correlated significantly with g at age 4 (r = .33, p < .001, n = 14,050) and with g at age 14 (r = .20, p < .001, n = 4,622). The genetic correlation between drawing at age 4 and g at age 14 was .52, 95% confidence interval = [.31, .75]. Individual differences in this widespread behavior have an important genetic component and a significant genetic link with g. © The Author(s) 2014.

Genetic and phenotypic relationships between and within support and demand tissues in a single line of broiler chicken.

PubMed

Rance, K A; McEntee, G M; McDevitt, R M

2002-09-01

1. With commercial selection for increased broiler performance there has been a correlated increase in the incidence of several metabolic disorders. A study was undertaken to investigate the balance between the unselected support tissues (including the heart, liver, spleen and the components of the gastrointestinal tract (GIT)) which drive growth in the selected demand tissues (eviscerated body mass) by assessing the genetic correlations between these traits. 2. Data were collected on 483 broiler birds taken from a commercial male broiler line with pedigree information. 3. Genetic parameters were estimated by restricted maximum likelihood with an individual animal model. Heritability estimates for the production traits ranged between h2 = 0.48 and 0.59 for leg and breast mass, respectively. The support tissues were generally associated with low to moderate heritabilities ranging between h2 = 0.19 for proventriculus to h2 = 0.38 for duodenum mass, although moderately high heritability estimates (h2 = 0.51 to 0.54) were associated with the spleen and gizzard. 4. The genetic correlations between production traits and support organs were generally low, however, heart mass was positively correlated with all carcase components of the lean tissue mass; the genetic correlations ranged between r(g) = 0.55 with breast mass to r(g) = 0.64 with eviscerated body mass. 5. In general, there were strong positive genetic correlations between the different components of the GIT. Organs that have been implicated in the development of metabolic disorders such as ascites (for example, the heart) could theoretically be used in commercial selection indices due to moderate heritabilities (heart: h2 = 0.30) and favourable correlations with commercially important traits.

Does selection in a challenging environment produce Nile tilapia genotypes that can thrive in a range of production systems?

PubMed

Thoa, Ngo Phu; Ninh, Nguyen Huu; Knibb, Wayne; Nguyen, Nguyen Hong

2016-02-19

This study assessed whether selection for high growth in a challenging environment of medium salinity produces tilapia genotypes that perform well across different production environments. We estimated the genetic correlations between trait expressions in saline and freshwater using a strain of Nile tilapia selected for fast growth under salinity water of 15-20 ppt. We also estimated the heritability and genetic correlations for new traits of commercial importance (sexual maturity, feed conversion ratio, deformity and gill condition) in a full pedigree comprising 36,145 fish. The genetic correlations for the novel characters between the two environments were 0.78-0.99, suggesting that the effect of genotype by environment interaction was not biologically important. Across the environments, the heritability for body weight was moderate to high (0.32-0.62), indicating that this population will continue responding to future selection. The estimates of heritability for sexual maturity and survival were low but significant. The additive genetic components also exist for FCR, gill condition and deformity. Genetic correlations of harvest body weight with sexual maturity were positive and those between harvest body weight with FCR were negative. Our results indicate that the genetic line selected under a moderate saline water environment can be cultured successfully in freshwater systems.

Freezability genetics in rabbit semen.

PubMed

Lavara, R; Mocé, E; Baselga, M; Vicente, J S

2017-10-15

The aim of this study was to estimate the heritability of semen freezability and to estimate the genetic correlation between frozen-thawed sperm traits and the growth rate in a paternal rabbit line. Estimated heritabilities showed that frozen-thawed semen traits are heritable (ranged between 0.08 and 0.15). In the case of Live-FT (percentage of viable sperm after freezing), the estimated heritability is the highest one, and suggests the possibility of effective selection. After the study of genetic correlations it seems that daily weight gain (DG) was negatively correlated with sperm freezability, but no further conclusions could be drawn due to the high HPD95%. More data should be included in order to obtain better accuracy for the estimates of these genetic correlations. If the results obtained at present study were confirmed, it would imply that selection for DG could alter sperm cell membranes or seminal plasma composition, both components related to sperm cryoresistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Phenotypic and genetic structure of traits delineating personality disorder.

PubMed

Livesley, W J; Jang, K L; Vernon, P A

1998-10-01

The evidence suggests that personality traits are hierarchically organized with more specific or lower-order traits combining to form more generalized higher-order traits. Agreement exists across studies regarding the lower-order traits that delineate personality disorder but not the higher-order traits. This study seeks to identify the higher-order structure of personality disorder by examining the phenotypic and genetic structures underlying lower-order traits. Eighteen lower-order traits were assessed using the Dimensional Assessment of Personality Disorder-Basic Questionnaire in samples of 656 personality disordered patients, 939 general population subjects, and a volunteer sample of 686 twin pairs. Principal components analysis yielded 4 components, labeled Emotional Dysregulation, Dissocial Behavior, Inhibitedness, and Compulsivity, that were similar across the 3 samples. Multivariate genetic analyses also yielded 4 genetic and environmental factors that were remarkably similar to the phenotypic factors. Analysis of the residual heritability of the lower-order traits when the effects of the higher-order factors were removed revealed a substantial residual heritable component for 12 of the 18 traits. The results support the following conclusions. First, the stable structure of traits across clinical and nonclinical samples is consistent with dimensional representations of personality disorders. Second, the higher-order traits of personality disorder strongly resemble dimensions of normal personality. This implies that a dimensional classification should be compatible with normative personality. Third, the residual heritability of the lower-order traits suggests that the personality phenotypes are based on a large number of specific genetic components.

Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

PubMed Central

Mucci, Lorelei A.; Hjelmborg, Jacob B.; Harris, Jennifer R.; Czene, Kamila; Havelick, David J.; Scheike, Thomas; Graff, Rebecca E.; Holst, Klaus; Möller, Sören; Unger, Robert H.; McIntosh, Christina; Nuttall, Elizabeth; Brandt, Ingunn; Penney, Kathryn L.; Hartman, Mikael; Kraft, Peter; Parmigiani, Giovanni; Christensen, Kaare; Koskenvuo, Markku; Holm, Niels V.; Heikkilä, Kauko; Pukkala, Eero; Skytthe, Axel; Adami, Hans-Olov; Kaprio, Jaakko

2017-01-01

Importance Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. Objective To estimate familial risk and heritability of cancer types in a large twin cohort. Design, Setting, and Participants Prospective study of 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. Exposures Shared environmental and heritable risk factors among pairs of twins. Main Outcomes and Measures The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. Results A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). Conclusions and Relevance In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling. PMID:26746459

Progression of lumbar disc degeneration over a decade: a heritability study

PubMed Central

Williams, Frances M K; Popham, Maria; Sambrook, Philip N; Jones, Annette F; Spector, Tim D; MacGregor, Alex J

2011-01-01

Objectives Lumbar disc degeneration (LDD) is prevalent, age-related and contributes to low back pain. Cross-sectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors. Methods A 10-year follow-up of MRI-determined LDD was performed in 234 pairs of twin volunteers in the UK and Australia, comprising 90 monozygotic pairs and 144 dizygotic same-sex twin pairs. Of the total sample, 95% were female. The mean age at baseline was 53.3 years (range 32.3–69.5). The rate of progression was calculated and, because the effect of age was non-linear, the sample was divided into age strata and heritability estimated for each trait's progression. Results All MRI-determined traits worsened significantly over the period of follow-up (p<0.0001 for each). Change in disc height was not heritable at any age while posterior disc bulge was heritable across all age categories (range 28–53%), with higher heritability in those over 60 years. Change in disc signal intensity and anterior osteophytes were found to be heritable only in those aged under 50 years at baseline (heritability estimates 76% (95% CI 44% to 100%) and 74% (42% to 100%), respectively). Conclusions Longitudinal change in LDD traits is heritable for all traits except disc height, but there is a significant influence of age, which varies across traits. Future studies to define the genetic variants influencing LDD progression should examine MRI traits individually and in women should focus on those under 50 years of age. PMID:21402564

Genetic parameters of body weight and ascites in broilers: effect of different incidence rates of ascites syndrome.

PubMed

Ahmadpanah, J; Ghavi Hossein-Zadeh, N; Shadparvar, A A; Pakdel, A

2017-02-01

1. The objectives of the current study were to investigate the effect of incidence rate (5%, 10%, 20%, 30% and 50%) of ascites syndrome on the expression of genetic characteristics for body weight at 5 weeks of age (BW5) and AS and to compare different methods of genetic parameter estimation for these traits. 2. Based on stochastic simulation, a population with discrete generations was created in which random mating was used for 10 generations. Two methods of restricted maximum likelihood and Bayesian approach via Gibbs sampling were used for the estimation of genetic parameters. A bivariate model including maternal effects was used. The root mean square error for direct heritabilities was also calculated. 3. The results showed that when incidence rates of ascites increased from 5% to 30%, the heritability of AS increased from 0.013 and 0.005 to 0.110 and 0.162 for linear and threshold models, respectively. 4. Maternal effects were significant for both BW5 and AS. Genetic correlations were decreased by increasing incidence rates of ascites in the population from 0.678 and 0.587 at 5% level of ascites to 0.393 and -0.260 at 50% occurrence for linear and threshold models, respectively. 5. The RMSE of direct heritability from true values for BW5 was greater based on a linear-threshold model compared with the linear model of analysis (0.0092 vs. 0.0015). The RMSE of direct heritability from true values for AS was greater based on a linear-linear model (1.21 vs. 1.14). 6. In order to rank birds for ascites incidence, it is recommended to use a threshold model because it resulted in higher heritability estimates compared with the linear model and that BW5 could be one of the main components of selection goals.

Effects of genotype and environment on the contents of betaine, choline, and trigonelline in cereal grains.

PubMed

Corol, Delia-Irina; Ravel, Catherine; Raksegi, Mariann; Bedo, Zoltan; Charmet, Gilles; Beale, Michael H; Shewry, Peter R; Ward, Jane L

2012-05-30

This study examined the environmental and genetic variation in methyl donor contents and compositions of 200 cereal genotypes. Glycine betaine, choline, and trigonelline contents were determined by (1)H NMR, and significant differences were observed between cereal types (G) and across harvesting years and growing locations (E). Glycine betaine was the most abundant methyl donor in all of the 200 lines grown on a single site, and concentrations ranged from 0.43 ± 0.09 mg/g dm in oats to 2.57 ± 0.25 mg/g dm in diploid Einkorn varieties. In bread wheat genotypes there was a 3-fold difference in glycine betaine content. Choline contents, in the same lines, were substantially lower, and mean concentrations ranged from 0.17 mg/g dm in oats to 0.27 mg/g dm in durum wheat. Trigonelline was by far the least abundant of the methyl donors studied. Despite this, however, there were large differences between cereal types. Twenty-six wheat genotypes were grown in additional years at four European locations. The average glycine betaine content was highest in grains grown in Hungary and lowest in those grown in the United Kingdom. Across the six environments, there was a 3.8-fold difference in glycine betaine content. Glycine betaine levels, although moderately heritable (0.36), were found to be the most susceptible to the environmental conditions. Free choline concentrations were less variable across genotypes, but heritability of this component was the lowest of all methyl donor components (0.25) and showed a high G × E interaction. Trigonelline showed the most variation due to genotype. Heritability of this metabolite was the highest (0.59), but given that it is at a very low concentration in wheat, it is probably not attractive to plant breeders.

Genetic mixed linear models for twin survival data.

PubMed

Ha, Il Do; Lee, Youngjo; Pawitan, Yudi

2007-07-01

Twin studies are useful for assessing the relative importance of genetic or heritable component from the environmental component. In this paper we develop a methodology to study the heritability of age-at-onset or lifespan traits, with application to analysis of twin survival data. Due to limited period of observation, the data can be left truncated and right censored (LTRC). Under the LTRC setting we propose a genetic mixed linear model, which allows general fixed predictors and random components to capture genetic and environmental effects. Inferences are based upon the hierarchical-likelihood (h-likelihood), which provides a statistically efficient and unified framework for various mixed-effect models. We also propose a simple and fast computation method for dealing with large data sets. The method is illustrated by the survival data from the Swedish Twin Registry. Finally, a simulation study is carried out to evaluate its performance.

Laboratory Estimates of Heritabilities and Genetic Correlations in Nature

PubMed Central

Riska, B.; Prout, T.; Turelli, M.

1989-01-01

A lower bound on heritability in a natural environment can be determined from the regression of offspring raised in the laboratory on parents raised in nature. An estimate of additive genetic variance in the laboratory is also required. The estimated lower bounds on heritabilities can sometimes be used to demonstrate a significant genetic correlation between two traits in nature, if their genetic and phenotypic correlations in nature have the same sign, and if sample sizes are large, and heritabilities and phenotypic and genetic correlations are high. PMID:2515111

Genetics of serum carotenoid concentrations and their correlation with obesity-related traits in Mexican American children.

PubMed

Farook, Vidya S; Reddivari, Lavanya; Mummidi, Srinivas; Puppala, Sobha; Arya, Rector; Lopez-Alvarenga, Juan Carlos; Fowler, Sharon P; Chittoor, Geetha; Resendez, Roy G; Kumar, Birunda Mohan; Comuzzie, Anthony G; Curran, Joanne E; Lehman, Donna M; Jenkinson, Christopher P; Lynch, Jane L; DeFronzo, Ralph A; Blangero, John; Hale, Daniel E; Duggirala, Ravindranath; Vanamala, Jairam Kp

2017-07-01

Background: Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children. Objective: We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children. Design: Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and β-carotenoid concentrations were measured in ∼570 (α-carotene in 565 and β-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex. Results: Carotenoid concentrations were highly heritable and significant [α-carotene: heritability ( h 2 ) = 0.81, P = 6.7 × 10 -11 ; β-carotene: h 2 = 0.90, P = 3.5 × 10 -15 ]. After adjusting for multiple comparisons, we found significant ( P ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; β-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; β-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant ( P = 0.051) genetic correlations only between β-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant. Conclusions: The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence β-carotene and obesity and lipid traits in MA children. © 2017 American Society for Nutrition.

Heritability of MMPI-2 scales in the UCSF Family Alcoholism Study

PubMed Central

Gizer, Ian R.; Seaton-Smith, Kimberley L.; Ehlers, Cindy L.; Vietan, Cassandra; Wilhelmsen, Kirk C.

2009-01-01

The present study evaluated the heritability of personality traits and psychopathology symptoms assessed by the Minnesota Multiphasic Personality Interview 2nd edition (MMPI-2) in a family-based sample selected for alcohol dependence. Participants included 950 probands and 1204 first-degree relatives recruited for the UCSF Family Alcoholism Study. Heritability estimates (h2) for MMPI-2 scales ranged from .25–.49. When alcohol dependence was used as a covariate, heritability estimates remained significant but generally declined. However, when the MMPI-2 scales were used as covariates to estimate the heritability of alcohol dependence, scales measuring antisocial behavior (ASP), depressive symptoms (DEP), and addictive behavior (MAC-R) led to moderate increases in the heritability of alcohol dependence. This suggests that the ASP, DEP, and MAC-R scales may explain some of the non-genetic variance in the alcohol dependence diagnosis in this population when utilized as covariates, and thus may serve to produce a more homogeneous and heritable alcohol dependence phenotype. PMID:20390702

Partitioning heritability by functional annotation using genome-wide association summary statistics.

PubMed

Finucane, Hilary K; Bulik-Sullivan, Brendan; Gusev, Alexander; Trynka, Gosia; Reshef, Yakir; Loh, Po-Ru; Anttila, Verneri; Xu, Han; Zang, Chongzhi; Farh, Kyle; Ripke, Stephan; Day, Felix R; Purcell, Shaun; Stahl, Eli; Lindstrom, Sara; Perry, John R B; Okada, Yukinori; Raychaudhuri, Soumya; Daly, Mark J; Patterson, Nick; Neale, Benjamin M; Price, Alkes L

2015-11-01

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.

From cow to cheese: genetic parameters of the flavour fingerprint of cheese investigated by direct-injection mass spectrometry (PTR-ToF-MS).

PubMed

Bergamaschi, Matteo; Cecchinato, Alessio; Biasioli, Franco; Gasperi, Flavia; Martin, Bruno; Bittante, Giovanni

2016-11-16

Volatile organic compounds determine important quality traits in cheese. The aim of this work was to infer genetic parameters of the profile of volatile compounds in cheese as revealed by direct-injection mass spectrometry of the headspace gas from model cheeses that were produced from milk samples from individual cows. A total of 1075 model cheeses were produced using raw whole-milk samples that were collected from individual Brown Swiss cows. Single spectrometry peaks and a combination of these peaks obtained by principal component analysis (PCA) were analysed. Using a Bayesian approach, we estimated genetic parameters for 240 individual spectrometry peaks and for the first ten principal components (PC) extracted from them. Our results show that there is some genetic variability in the volatile compound fingerprint of these model cheeses. Most peaks were characterized by a substantial heritability and for about one quarter of the peaks, heritability (up to 21.6%) was higher than that of the best PC. Intra-herd heritability of the PC ranged from 3.6 to 10.2% and was similar to heritabilities estimated for milk fat, specific fatty acids, somatic cell count and some coagulation parameters in the same population. We also calculated phenotypic correlations between PC (around zero as expected), the corresponding genetic correlations (from -0.79 to 0.86) and correlations between herds and sampling-processing dates (from -0.88 to 0.66), which confirmed that there is a relationship between cheese flavour and the dairy system in which cows are reared. This work reveals the existence of a link between the cow's genetic background and the profile of volatile compounds in cheese. Analysis of the relationships between the volatile organic compound (VOC) content and the sensory characteristics of cheese as perceived by the consumer, and of the genetic basis of these relationships could generate new knowledge that would open up the possibility of controlling and improving the sensory properties of cheese through genetic selection of cows. More detailed investigations are necessary to connect VOC with the sensory properties of cheese and gain a better understanding of the significance of these new phenotypes.

Genetic influences on bone loss in the San Antonio Family Osteoporosis Study

PubMed Central

Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

2009-01-01

Summary The genetic contribution to age-related bone loss is not well understood. We estimated that genes accounted for 25–45% of variation in 5-year change in bone mineral density in men and women. An autosome-wide linkage scan yielded no significant evidence for chromosal regions implicated in bone loss. Introduction The contribution of genetics to acquisition of peak bone mass is well documented, but little is know about the influence of genes on subsequent bone loss with age. We therefore measured 5-year change in bone mineral density (BMD) in 300 Mexican Americans (>45 years of age) from the San Antonio Family Osteoporosis Study to identify genetic factors influencing bone loss. Methods Annualized change in BMD was calculated from measurements taken 5.5 years apart. Heritability (h2) of BMD change was estimated using variance components methods and autosome-wide linkage analysis was carried out using 460 microsatellite markers at a mean 7.6 cM interval density. Results Rate of BMD change was heritable at the forearm (h2=0.31, p=0.021), hip (h2 =0.44, p=0.017), spine (h2=0.42, p=0.005), but not whole body (h2=0.18, p=0.123). Covariates associated with rapid bone loss (advanced age, baseline BMD, female sex, low baseline weight, postmenopausal status, and interim weight loss) accounted for 10% to 28% of trait variation. No significant evidence of linkage was observed at any skeletal site. Conclusions This is one of the first studies to report significant heritability of BMD change for weight-bearing and non-weight-bearing bones in an unselected population and the first linkage scan for change in BMD. PMID:18414963

A twin-sibling study on the relationship between exercise attitudes and exercise behavior.

PubMed

Huppertz, Charlotte; Bartels, Meike; Jansen, Iris E; Boomsma, Dorret I; Willemsen, Gonneke; de Moor, Marleen H M; de Geus, Eco J C

2014-01-01

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18-50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R(2) = 28 %). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but two unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins' difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.

A Twin-Sibling Study on the Relationship Between Exercise Attitudes and Exercise Behavior

PubMed Central

Bartels, Meike; Jansen, Iris E.; Boomsma, Dorret I.; Willemsen, Gonneke; de Moor, Marleen H. M.; de Geus, Eco J. C.

2013-01-01

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin–sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18–50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R2 = 28 %). Bivariate modeling further showed that all the genetic (0.36 <|rA| <0.80) and all but two unique environmental (0.00 <|rE| <0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins’ difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior. PMID:24072598

Heritability of and mortality prediction with a longevity phenotype: the healthy aging index.

PubMed

Sanders, Jason L; Minster, Ryan L; Barmada, M Michael; Matteini, Amy M; Boudreau, Robert M; Christensen, Kaare; Mayeux, Richard; Borecki, Ingrid B; Zhang, Qunyuan; Perls, Thomas; Newman, Anne B

2014-04-01

Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study. The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model. Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring. The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

Plastic and Heritable Components of Phenotypic Variation in Nucella lapillus: An Assessment Using Reciprocal Transplant and Common Garden Experiments

PubMed Central

Pascoal, Sonia; Carvalho, Gary; Creer, Simon; Rock, Jenny; Kawaii, Kei; Mendo, Sonia; Hughes, Roger

2012-01-01

Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F2s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F1s than F2s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal. PMID:22299035

Plastic and heritable components of phenotypic variation in Nucella lapillus: an assessment using reciprocal transplant and common garden experiments.

PubMed

Pascoal, Sonia; Carvalho, Gary; Creer, Simon; Rock, Jenny; Kawaii, Kei; Mendo, Sonia; Hughes, Roger

2012-01-01

Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F(2)s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F(1)s than F(2)s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal.

Detection of gene-environment interaction in pedigree data using genome-wide genotypes.

PubMed

Nivard, Michel G; Middeldorp, Christel M; Lubke, Gitta; Hottenga, Jouke-Jan; Abdellaoui, Abdel; Boomsma, Dorret I; Dolan, Conor V

2016-12-01

Heritability may be estimated using phenotypic data collected in relatives or in distantly related individuals using genome-wide single nucleotide polymorphism (SNP) data. We combined these approaches by re-parameterizing the model proposed by Zaitlen et al and extended this model to include moderation of (total and SNP-based) genetic and environmental variance components by a measured moderator. By means of data simulation, we demonstrated that the type 1 error rates of the proposed test are correct and parameter estimates are accurate. As an application, we considered the moderation by age or year of birth of variance components associated with body mass index (BMI), height, attention problems (AP), and symptoms of anxiety and depression. The genetic variance of BMI was found to increase with age, but the environmental variance displayed a greater increase with age, resulting in a proportional decrease of the heritability of BMI. Environmental variance of height increased with year of birth. The environmental variance of AP increased with age. These results illustrate the assessment of moderation of environmental and genetic effects, when estimating heritability from combined SNP and family data. The assessment of moderation of genetic and environmental variance will enhance our understanding of the genetic architecture of complex traits.

Evidence for higher heritability of somatotype compared to body mass index in female twins.

PubMed

Reis, Victor Machado; Machado, João V; Fortes, Marcos S; Fernandes, Paula Roquetti; Silva, António José; Dantas, Paulo Silva; Filho, José Fernandes

2007-01-01

The influence of genetics on human physique and obesity has been addressed by the literature. Evidence for heritability of anthropometric characteristics has been previously described, mainly for the body mass index (BMI). However, few studies have investigated the influence of genetics on the Heath-Carter somatotype. The aim of the present study was to assess the heritability of BMI and somatotype (endomorphy, mesomorphy, and ectomorphy) in a group of female monozygotic and dizygotic twins from childhood to early adulthood. A total of 28 females aged from 7 to 19 years old were studied. The group included 5 monozygotic and 9 dizygotic pairs of twins. The heritability was assessed by the twin method (h(2)). The anthropometric measures and somatotype were assessed using standard validated procedures. Significant differences between monozygotic and dizygotic pairs of twins were found for height, endomorphy, ectomorphy, and mesomorphy, and the heritability for these measures was high (h(2) between 0.88 and 0.97). No significant differences were found between monozygotic and dizygotic twins for weight, and the BMI and the heritability indexes were lower for these measures (respectively 0.42 and 0.52). The results of the present study have indicated that the somatotype may be more sensible to genetic influences than the BMI in females.

Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

PubMed

Morrow, E H; Leijon, A; Meerupati, A

2008-11-01

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

Heritability and familiality of neurological soft signs: evidence from healthy twins, patients with schizophrenia and non-psychotic first-degree relatives.

PubMed

Xu, T; Wang, Y; Li, Z; Huang, J; Lui, S S Y; Tan, S-P; Yu, X; Cheung, E F C; He, M-G; Ott, J; Gur, R E; Gur, R C; Chan, R C K

2016-01-01

Neurological soft signs (NSS) have long been considered potential endophenotypes for schizophrenia. However, few studies have investigated the heritability and familiality of NSS. The present study examined the heritability and familiality of NSS in healthy twins and patient-relative pairs. The abridged version of the Cambridge Neurological Inventory was administered to 267 pairs of monozygotic twins, 124 pairs of dizygotic twins, and 75 pairs of patients with schizophrenia and their non-psychotic first-degree relatives. NSS were found to have moderate but significant heritability in the healthy twin sample. Moreover, patients with schizophrenia correlated closely with their first-degree relatives on NSS. Taken together, the findings provide evidence on the heritability and familiality of NSS in the Han Chinese population.

Screening and treatment for heritable thrombophilia in pregnancy failure: inconsistencies among UK early pregnancy units.

PubMed

Norrie, Gillian; Farquharson, Roy G; Greaves, Mike

2009-01-01

The significance of heritable thrombophilia in pregnancy failure is controversial. We surveyed all UK Early Pregnancy Units and 70% responded. The majority test routinely for heritable thrombophilias; 80%, 76% and 88% undertook at least one screening test in late miscarriage, recurrent miscarriage and placental abruption, respectively. The range of thrombophilias sought is inconsistent: testing for proteins C and S deficiency and F5 R506Q (factor V Leiden) is most prevalent. Detection of heritable thrombophilia frequently leads to administration of antithrombotics in subsequent pregnancies. Thus, thrombophilia testing and use of antithrombotics are widespread in the UK despite controversies regarding the role of heritable thrombophilia in the pathogenesis of pregnancy complications, and the lack of robust evidence for the efficacy of antithrombotic therapy.

Does selection in a challenging environment produce Nile tilapia genotypes that can thrive in a range of production systems?

PubMed Central

Thoa, Ngo Phu; Ninh, Nguyen Huu; Knibb, Wayne; Nguyen, Nguyen Hong

2016-01-01

This study assessed whether selection for high growth in a challenging environment of medium salinity produces tilapia genotypes that perform well across different production environments. We estimated the genetic correlations between trait expressions in saline and freshwater using a strain of Nile tilapia selected for fast growth under salinity water of 15–20 ppt. We also estimated the heritability and genetic correlations for new traits of commercial importance (sexual maturity, feed conversion ratio, deformity and gill condition) in a full pedigree comprising 36,145 fish. The genetic correlations for the novel characters between the two environments were 0.78–0.99, suggesting that the effect of genotype by environment interaction was not biologically important. Across the environments, the heritability for body weight was moderate to high (0.32–0.62), indicating that this population will continue responding to future selection. The estimates of heritability for sexual maturity and survival were low but significant. The additive genetic components also exist for FCR, gill condition and deformity. Genetic correlations of harvest body weight with sexual maturity were positive and those between harvest body weight with FCR were negative. Our results indicate that the genetic line selected under a moderate saline water environment can be cultured successfully in freshwater systems. PMID:26892814

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

PubMed Central

Wheeler, William A.; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Figueroa, Jonine D.; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; Vivo, Immaculata De; McGlynn, Katherine A.; Purdue, Mark P.; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Angelucci, Emanuele; Ansell, Stephen M.; Arici, Cecilia; Armstrong, Bruce K.; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A.; Birmann, Brenda M.; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brinton, Louise; Brooks-Wilson, Angela R.; Bueno-de-Mesquita, H. Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K. C.; Chang, Ellen T.; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C.; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S.; Comperat, Eva; Conde, Lucia; Connors, Joseph M.; Conti, David; Cortessis, Victoria K.; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G.; Ding, Ti; Diver, W. Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J.; Ennas, Maria Grazia; Erickson, Ralph L.; Feychting, Maria; Flanagan, Adrienne M.; Foretova, Lenka; Fraumeni, Joseph F.; Freedman, Neal D.; Beane Freeman, Laura E.; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D.; Gastier-Foster, Julie; Gaudet, Mia M.; Gaziano, J. Michael; Giffen, Carol; Giles, Graham G.; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M.; Haiman, Christopher A.; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R.; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Horn-Ross, Pamela L.; Hosain, G. M. Monawar; Hosgood, H. Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D.; Jackson, Rebecca D.; Jacobs, Eric J.; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R.; Kelly, Rachel S.; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert J.; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M.; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S.; Link, Brian K.; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S.; Michaud, Dominique S.; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E.; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Oberg, Ann L.; Offit, Kenneth; Oh, In-Jae; Olson, Sara H.; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A.; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M.; de Sanjose, Silvia; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K.; Shanafelt, Tait D.; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Spinelli, John J.; Staines, Anthony; Stampfer, Meir; Stern, Marianna C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael S.; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A.; Tinker, Lesley F.; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C. H.; Villano, Danylo J.; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J.; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M.; Cerhan, James R.; Ferri, Giovanni M.; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M.; Smedby, Karin E.; Teras, Lauren R.; Vijai, Joseph; Wang, Sophia S.; Brennan, Paul; Caporaso, Neil E.; Hunter, David J.; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T.; Slager, Susan L.; Chanock, Stephen J.; Chatterjee, Nilanjan

2015-01-01

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. PMID:26464424

Quantitative genetics of ultrasonic advertisement signalling in the lesser waxmoth Achroia grisella (Lepidoptera: pyralidae).

PubMed

Collins, R D; Jang, Y; Reinhold, K; Greenfield, M D

1999-12-01

Males of the lesser waxmoth Achroia grisella (Lepidoptera: Pyralidae) produce ultrasonic advertisement signals attractive to females within several metres. Previous studies showed that females prefer male signals that are louder, delivered at a faster rate, and have a greater asynchrony between pulses produced by the right and left wings. These three signal characters vary considerably within populations but are repeatable within individuals. Breeding experiments employing half-sib designs were conducted on both collectively and individually reared moths to determine genetic variance within and covariance among these signal characters. Heritabilities of all signal characters were significant among collectively reared moths. Heritabilities for signal rate and right-left wing asynchrony interval were not significant, however, among individually reared moths, suggesting the presence of significant nonadditive genetic variance or common environmental variation. Development time was also significantly heritable, but only under individual rearing. The only significant genetic correlation was between signal rate and length of the right-left wing asynchrony and this was negative. Our findings on heritability of signal characters are consistent with a coevolutionary sexual selection mechanism, but the absence of signal x development genetic correlation fails to support specifically a good-genes mechanism. The variation in heritability among conditions suggests that environmental variance may be high, and may render selection on signal characters by female choice ineffective. Thus, additive genetic variance for these characters may be maintained in the presence of directional female choice.

SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE.

PubMed

Docherty, A R; Moscati, A; Peterson, R; Edwards, A C; Adkins, D E; Bacanu, S A; Bigdeli, T B; Webb, B T; Flint, J; Kendler, K S

2016-10-25

Biometrical genetic studies suggest that the personality dimensions, including neuroticism, are moderately heritable (~0.4 to 0.6). Quantitative analyses that aggregate the effects of many common variants have recently further informed genetic research on European samples. However, there has been limited research to date on non-European populations. This study examined the personality dimensions in a large sample of Han Chinese descent (N=10 064) from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology study, aimed at identifying genetic risk factors for recurrent major depression among a rigorously ascertained cohort. Heritability of neuroticism as measured by the Eysenck Personality Questionnaire (EPQ) was estimated to be low but statistically significant at 10% (s.e.=0.03, P=0.0001). In addition to EPQ, neuroticism based on a three-factor model, data for the Big Five (BF) personality dimensions (neuroticism, openness, conscientiousness, extraversion and agreeableness) measured by the Big Five Inventory were available for controls (n=5596). Heritability estimates of the BF were not statistically significant despite high power (>0.85) to detect heritabilities of 0.10. Polygenic risk scores constructed by best linear unbiased prediction weights applied to split-half samples failed to significantly predict any of the personality traits, but polygenic risk for neuroticism, calculated with LDpred and based on predictive variants previously identified from European populations (N=171 911), significantly predicted major depressive disorder case-control status (P=0.0004) after false discovery rate correction. The scores also significantly predicted EPQ neuroticism (P=6.3 × 10 -6 ). Factor analytic results of the measures indicated that any differences in heritabilities across samples may be due to genetic variation or variation in haplotype structure between samples, rather than measurement non-invariance. Findings demonstrate that neuroticism can be significantly predicted across ancestry, and highlight the importance of studying polygenic contributions to personality in non-European populations.

Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

PubMed

Herbeth, Bernard; Samara, Anastasia; Ndiaye, Coumba; Marteau, Jean-Brice; Berrahmoune, Hind; Siest, Gérard; Visvikis-Siest, Sophie

2010-06-03

We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters "risk lipids" and "protective lipids". Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: "liver enzymes", "adiposity/blood pressure" and "inflammation". Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits. Copyright 2010 Elsevier B.V. All rights reserved.

Quantitative trait loci identified for blood chemistry components of an advanced intercross line of chickens under heat stress.

PubMed

Van Goor, Angelica; Ashwell, Christopher M; Persia, Michael E; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

2016-04-14

Heat stress in poultry results in considerable economic losses and is a concern for both animal health and welfare. Physiological changes occur during periods of heat stress, including changes in blood chemistry components. A highly advanced intercross line, created from a broiler (heat susceptible) by Fayoumi (heat resistant) cross, was exposed to daily heat cycles for seven days starting at 22 days of age. Blood components measured pre-heat treatment and on the seventh day of heat treatment included pH, pCO2, pO2, base excess, HCO3, TCO2, K, Na, ionized Ca, hematocrit, hemoglobin, sO2, and glucose. A genome-wide association study (GWAS) for these traits and their calculated changes was conducted to identify quantitative trait loci (QTL) using a 600 K SNP panel. There were significant increases in pH, base excess, HCO3, TCO2, ionized Ca, hematocrit, hemoglobin, and sO2, and significant decreases in pCO2 and glucose after 7 days of heat treatment. Heritabilities ranged from 0.01-0.21 for pre-heat measurements, 0.01-0.23 for measurements taken during heat, and 0.00-0.10 for the calculated change due to heat treatment. All blood components were highly correlated within measurement days, but not correlated between measurement days. The GWAS revealed 61 QTL for all traits, located on GGA (Gallus gallus chromosome) 1, 3, 6, 9, 10, 12-14, 17, 18, 21-28, and Z. A functional analysis of the genes in these QTL regions identified the Angiopoietin pathway as significant. The QTL that co-localized for three or more traits were on GGA10, 22, 26, 28, and Z and revealed candidate genes for birds' response to heat stress. The results of this study contribute to our knowledge of levels and heritabilities of several blood components of chickens under thermoneutral and heat stress conditions. Most components responded to heat treatment. Mapped QTL may serve as markers for genomic selection to enhance heat tolerance in poultry. The Angiopoietin pathway is likely involved in the response to heat stress in chickens. Several candidate genes were identified, giving additional insight into potential mechanisms of physiologic response to high ambient temperatures.

Genetic association of impulsivity in young adults: a multivariate study

PubMed Central

Khadka, S; Narayanan, B; Meda, S A; Gelernter, J; Han, S; Sawyer, B; Aslanzadeh, F; Stevens, M C; Hawkins, K A; Anticevic, A; Potenza, M N; Pearlson, G D

2014-01-01

Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype–phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors. PMID:25268255

Effects of selection for blood serum IGF-I concentration on reproductive performance of female Angus beef cattle.

PubMed

Zhang, X; Davis, M E; Moeller, S J; Ottobre, J S

2013-09-01

Reproductive performance of animals affects lifetime productivity. However, improvement of reproductive traits via direct selection is generally slow due to low heritability. Therefore, identification of indicator traits for reproductive performance may enhance genetic response. Previous studies showed that serum IGF-I concentration is a candidate indicator for growth and reproductive traits. The objective of our study was to estimate the variances or covariances of IGF-I concentration with reproductive traits. Data were collected from a divergent selection experiment for serum IGF-I concentration at the Eastern Agricultural Research Station owned by The Ohio State University. The study included a total of 2,662 calves in the 1989 to 2005 calf crops. Variance or covariance components were estimated for direct and maternal genetic effects, maternal environment effects, environment effects, and phenotypic effects using an animal model in a multiple-trait, derivative-free, restricted maximum likelihood (MTDFREML, Boldman et al., 1995) computer program. Direct additive genetic correlations suggest that selection for greater IGF-I concentration (heritability = 0.50 ± 0.07) could lead to increased conception rate (heritability = 0.11 ± 0.06, r = 0.32, P < 0.001) and calving rate (heritability = 0.13 ± 0.06, r = 0.43, P < 0.001) and decreased age at first calving in heifers (heritability = 0.35 ± 0.20, r = -0.40, P < 0.001).

Shared Environment Estimates for Educational Attainment: A Puzzle and Possible Solutions.

PubMed

Freese, Jeremy; Jao, Yu-Han

2017-02-01

Classical behavioral genetics models for twin and other family designs decompose traits into heritability, shared environment, and nonshared environment components. Estimates of heritability of adult traits are pervasively observed to be far higher than those of shared environment, which has been used to make broad claims about the impotence of upbringing. However, the most commonly studied nondemographic variable in many areas of social science, educational attainment, exhibits robustly high estimates both for heritability and for shared environment. When previously noticed, the usual explanation has emphasized family resources, but evidence suggests this is unlikely to explain the anomalous high estimates for shared environment of educational attainment. We articulate eight potential complementary explanations and discuss evidence of their prospective contributions to resolving the puzzle. In so doing, we hope to further consideration of how behavioral genetics findings may advance studies of social stratification beyond the effort to articulate specific genetic influences. © 2015 Wiley Periodicals, Inc.

A Combined Pathway and Regional Heritability Analysis Indicates NETRIN1 Pathway Is Associated With Major Depressive Disorder.

PubMed

Zeng, Yanni; Navarro, Pau; Fernandez-Pujals, Ana M; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Wray, Naomi R; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2017-02-15

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk. We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested. In GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model. These post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing.

PubMed

Tan, Cheng; Wu, Zhenfang; Ren, Jiangli; Huang, Zhuolin; Liu, Dewu; He, Xiaoyan; Prakapenka, Dzianis; Zhang, Ran; Li, Ning; Da, Yang; Hu, Xiaoxiang

2017-03-29

The number of teats in pigs is related to a sow's ability to rear piglets to weaning age. Several studies have identified genes and genomic regions that affect teat number in swine but few common results were reported. The objective of this study was to identify genetic factors that affect teat number in pigs, evaluate the accuracy of genomic prediction, and evaluate the contribution of significant genes and genomic regions to genomic broad-sense heritability and prediction accuracy using 41,108 autosomal single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing on 2936 Duroc boars. Narrow-sense heritability and dominance heritability of teat number estimated by genomic restricted maximum likelihood were 0.365 ± 0.030 and 0.035 ± 0.019, respectively. The accuracy of genomic predictions, calculated as the average correlation between the genomic best linear unbiased prediction and phenotype in a tenfold validation study, was 0.437 ± 0.064 for the model with additive and dominance effects and 0.435 ± 0.064 for the model with additive effects only. Genome-wide association studies (GWAS) using three methods of analysis identified 85 significant SNP effects for teat number on chromosomes 1, 6, 7, 10, 11, 12 and 14. The region between 102.9 and 106.0 Mb on chromosome 7, which was reported in several studies, had the most significant SNP effects in or near the PTGR2, FAM161B, LIN52, VRTN, FCF1, AREL1 and LRRC74A genes. This region accounted for 10.0% of the genomic additive heritability and 8.0% of the accuracy of prediction. The second most significant chromosome region not reported by previous GWAS was the region between 77.7 and 79.7 Mb on chromosome 11, where SNPs in the FGF14 gene had the most significant effect and accounted for 5.1% of the genomic additive heritability and 5.2% of the accuracy of prediction. The 85 significant SNPs accounted for 28.5 to 28.8% of the genomic additive heritability and 35.8 to 36.8% of the accuracy of prediction. The three methods used for the GWAS identified 85 significant SNPs with additive effects on teat number, including SNPs in a previously reported chromosomal region and SNPs in novel chromosomal regions. Most significant SNPs with larger estimated effects also had larger contributions to the total genomic heritability and accuracy of prediction than other SNPs.

Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium.

PubMed

Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In; Yi, Young Mi

2016-05-31

Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome.

Heritability of boldness and aggressiveness in the zebrafish.

PubMed

Ariyomo, Tolulope O; Carter, Mauricio; Watt, Penelope J

2013-03-01

Behavioural traits that are consistent over time and in different contexts are often referred to as personality traits. These traits influence fitness because they play a major role in foraging, reproduction and survival, and so it is assumed that they have little or no additive genetic variance and, consequently, low heritability because, theoretically, they are under strong selection. Boldness and aggressiveness are two personality traits that have been shown to affect fitness. By crossing single males to multiple females, we estimated the heritability of boldness and aggressiveness in the zebrafish, Danio rerio. The additive genetic variance was statistically significant for both traits and the heritability estimates (95 % confidence intervals) for boldness and aggressiveness were 0.76 (0.49, 0.90) and 0.36 (0.10, 0.72) respectively. Furthermore, there were significant maternal effects accounting for 18 and 9 % of the proportion of phenotypic variance in boldness and aggressiveness respectively. This study shows that there is a significant level of genetic variation in this population that would allow these traits to evolve in response to selection.

Heritable DNA methylation marks associated with susceptibility to breast cancer.

PubMed

Joo, Jihoon E; Dowty, James G; Milne, Roger L; Wong, Ee Ming; Dugué, Pierre-Antoine; English, Dallas; Hopper, John L; Goldgar, David E; Giles, Graham G; Southey, Melissa C

2018-02-28

Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable methylation marks associated with breast cancer susceptibility by studying 25 Australian multiple-case breast cancer families. Here we report genome-wide DNA methylation measured in 210 peripheral blood DNA samples provided by family members using the Infinium HumanMethylation450. We develop and apply a new statistical method to identify heritable methylation marks based on complex segregation analysis. We estimate carrier probabilities for the 1000 most heritable methylation marks based on family structure, and we use Cox proportional hazards survival analysis to identify 24 methylation marks with corresponding carrier probabilities significantly associated with breast cancer. We replicate an association with breast cancer risk for four of the 24 marks using an independent nested case-control study. Here, we report a novel approach for identifying heritable DNA methylation marks associated with breast cancer risk.

Describing the genetic architecture of epilepsy through heritability analysis.

PubMed

Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R

2014-10-01

Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Inheritance Analysis of Congenital Left Ventricular Outflow Tract Obstruction Malformations: Segregation, Multiplex Relative Risk, and Heritability

PubMed Central

McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.

2006-01-01

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347

Genome-wide association study of sporadic brain arteriovenous malformations.

PubMed

Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

2016-09-01

The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Detection of gene–environment interaction in pedigree data using genome-wide genotypes

PubMed Central

Nivard, Michel G; Middeldorp, Christel M; Lubke, Gitta; Hottenga, Jouke-Jan; Abdellaoui, Abdel; Boomsma, Dorret I; Dolan, Conor V

2016-01-01

Heritability may be estimated using phenotypic data collected in relatives or in distantly related individuals using genome-wide single nucleotide polymorphism (SNP) data. We combined these approaches by re-parameterizing the model proposed by Zaitlen et al and extended this model to include moderation of (total and SNP-based) genetic and environmental variance components by a measured moderator. By means of data simulation, we demonstrated that the type 1 error rates of the proposed test are correct and parameter estimates are accurate. As an application, we considered the moderation by age or year of birth of variance components associated with body mass index (BMI), height, attention problems (AP), and symptoms of anxiety and depression. The genetic variance of BMI was found to increase with age, but the environmental variance displayed a greater increase with age, resulting in a proportional decrease of the heritability of BMI. Environmental variance of height increased with year of birth. The environmental variance of AP increased with age. These results illustrate the assessment of moderation of environmental and genetic effects, when estimating heritability from combined SNP and family data. The assessment of moderation of genetic and environmental variance will enhance our understanding of the genetic architecture of complex traits. PMID:27436263

Correlation between Relatives given Complete Genotypes: from Identity by Descent to Identity by Function

PubMed Central

Sverdlov, Serge; Thompson, Elizabeth A.

2013-01-01

In classical quantitative genetics, the correlation between the phenotypes of individuals with unknown genotypes and a known pedigree relationship is expressed in terms of probabilities of IBD states. In existing approaches to the inverse problem where genotypes are observed but pedigree relationships are not, dependence between phenotypes is either modeled as Bayesian uncertainty or mapped to an IBD model via inferred relatedness parameters. Neither approach yields a relationship between genotypic similarity and phenotypic similarity with a probabilistic interpretation corresponding to a generative model. We introduce a generative model for diploid allele effect based on the classic infinite allele mutation process. This approach motivates the concept of IBF (Identity by Function). The phenotypic covariance between two individuals given their diploid genotypes is expressed in terms of functional identity states. The IBF parameters define a genetic architecture for a trait without reference to specific alleles or population. Given full genome sequences, we treat a gene-scale functional region, rather than a SNP, as a QTL, modeling patterns of dominance for multiple alleles. Applications demonstrated by simulation include phenotype and effect prediction and association, and estimation of heritability and classical variance components. A simulation case study of the Missing Heritability problem illustrates a decomposition of heritability under the IBF framework into Explained and Unexplained components. PMID:23851163

Effect of inclusion or non-inclusion of short lactations and cow and/or dam genetic group on genetic evaluation of Girolando dairy cattle.

PubMed

Canaza-Cayo, A W; Silva, M V G B; Cobuci, J A; Martins, M F; Lopes, P S

2016-04-04

The objective of this study was to evaluate the effects of inclusion or non-inclusion of short lactations and cow (CGG) and/or dam (DGG) genetic group on the genetic evaluation of 305-day milk yield (MY305), age at first calving (AFC), and first calving interval (FCI) of Girolando cows. Covariance components were estimated by the restricted maximum likelihood method in an animal model of single trait analyses. The heritability estimates for MY305, AFC, and FCI ranged from 0.23 to 0.29, 0.40 to 0.44, and 0.13 to 0.14, respectively, when short lactations were not included, and from 0.23 to 0.28, 0.39 to 0.43, and 0.13 to 0.14, respectively, when short lactations were included. The inclusion of short lactations caused little variation in the variance components and heritability estimates of traits, but their non-inclusion resulted in the re-ranking of animals. Models with CGG or DGG fixed effects had higher heritability estimates for all traits compared with models that consider these two effects simultaneously. We recommend using the model with fixed effects of CGG and inclusion of short lactations for the genetic evaluation of Girolando cattle.

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

PubMed

Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

2017-09-01

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Genetic and other risk factors for suicidal ideation and the relationship with depression.

PubMed

Dutta, R; Ball, H A; Siribaddana, S H; Sumathipala, A; Samaraweera, S; McGuffin, P; Hotopf, M

2017-10-01

There is a genetic contribution to the risk of suicide, but sparse prior research on the genetics of suicidal ideation. Active and passive suicidal ideation were assessed in a Sri Lankan population-based twin registry (n = 3906 twins) and a matched non-twin sample (n = 2016). Logistic regression models were used to examine associations with socio-demographic factors, environmental exposures and psychiatric symptoms. The heritability of suicidal ideation was assessed using structural equation modelling. The lifetime prevalence of any suicidal ideation was 13.0% (11.7-14.3%) for men; 21.8% (20.3-23.2%) for women, with no significant difference between twins and non-twins. Factors that predicted suicidal ideation included female gender, termination of marital relationship, low education level, urban residence, losing a parent whilst young, low standard of living and stressful life events in the preceding 12 months. Suicidal ideation was strongly associated with depression, but also with abnormal fatigue and alcohol and tobacco use. The best fitting structural equation model indicated a substantial contribution from genetic factors (57%; CI 47-66) and from non-shared environmental factors (43%; CI 34-53) in both men and women. In women this genetic component was largely mediated through depression, but in men there was a significant heritable component to suicidal ideation that was independent of depression. These are the first results to show a genetic contribution to suicidal ideation that is independent of depression outside of a high-income country. These phenomena may be generalizable, because previous research highlights similarities between the aetiology of mental disorders in Sri Lanka and higher-income countries.

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

PubMed Central

Havill, L.M.; Allen, M.R.; Bredbenner, T.L.; Burr, D.B.; Nicolella, D.P.; Turner, C.H.; Warren, D.M.; Mahaney, M.C.

2010-01-01

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2=0.58), toughness (h2=0.64), and BV/TV (h2=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures. PMID:19900599

Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents.

PubMed

Sieradzka, Dominika; Power, Robert A; Freeman, Daniel; Cardno, Alastair G; Dudbridge, Frank; Ronald, Angelica

2015-09-01

Occurrence of psychotic experiences is common amongst adolescents in the general population. Twin studies suggest that a third to a half of variance in adolescent psychotic experiences is explained by genetic influences. Here we test the extent to which common genetic variants account for some of the twin-based heritability. Psychotic experiences were assessed with the Specific Psychotic Experiences Questionnaire in a community sample of 2152 16-year-olds. Self-reported measures of Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms were obtained. Estimates of SNP heritability were derived and compared to the twin heritability estimates from the same sample. Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on pruned data. The standard GREML revealed a significant SNP heritability of 20 % for Anhedonia (SE = 0.12; p < 0.046) and an estimate of 19 % for Cognitive Disorganization, which was close to significant (SE = 0.13; p < 0.059). Grandiosity and Paranoia showed modest SNP heritability estimates (17 %; SE = 0.13 and 14 %; SE = 0.13, respectively, both n.s.), and zero estimates were found for Hallucinations and Negative Symptoms. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. SNP heritability estimates from the MAF-stratified approach were mostly consistent with the standard estimates and offered additional information about the distribution of heritability across the MAF range of the SNPs. In contrast, the estimates derived from the pruned data were for the most part not consistent with the other two approaches. It is likely that the difference seen in the pruned estimates was driven by the loss of tagged causal variants, an issue fundamental to this approach. The current results suggest that common genetic variants play a role in the etiology of some adolescent psychotic experiences, however further research on larger samples is desired and the use of MAF-stratified approach recommended.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

PubMed

Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; De Vivo, Immaculata; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Di Lollo, Simonetta; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Le Marchand, Loic; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

2015-12-01

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.

PubMed

Bertels, Frederic; Marzel, Alex; Leventhal, Gabriel; Mitov, Venelin; Fellay, Jacques; Günthard, Huldrych F; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Battegay, Manuel; Rauch, Andri; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Schmid, Patrick; Scherrer, Alexandra U; Müller, Viktor; Bonhoeffer, Sebastian; Kouyos, Roger; Regoes, Roland R

2018-01-01

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity

PubMed Central

Bertels, Frederic; Marzel, Alex; Leventhal, Gabriel; Mitov, Venelin; Fellay, Jacques; Günthard, Huldrych F; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Battegay, Manuel; Rauch, Andri; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Schmid, Patrick; Scherrer, Alexandra U; Müller, Viktor; Bonhoeffer, Sebastian; Kouyos, Roger; Regoes, Roland R

2018-01-01

Abstract Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence—measured as the rate of decline of CD4+ T cells—and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor–recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5–30%), and that of the per-parasite pathogenicity is 17% (4–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor. PMID:29029206

Genomic scan as a tool for assessing the genetic component of phenotypic variance in wild populations.

PubMed

Herrera, Carlos M

2012-01-01

Methods for estimating quantitative trait heritability in wild populations have been developed in recent years which take advantage of the increased availability of genetic markers to reconstruct pedigrees or estimate relatedness between individuals, but their application to real-world data is not exempt from difficulties. This chapter describes a recent marker-based technique which, by adopting a genomic scan approach and focusing on the relationship between phenotypes and genotypes at the individual level, avoids the problems inherent to marker-based estimators of relatedness. This method allows the quantification of the genetic component of phenotypic variance ("degree of genetic determination" or "heritability in the broad sense") in wild populations and is applicable whenever phenotypic trait values and multilocus data for a large number of genetic markers (e.g., amplified fragment length polymorphisms, AFLPs) are simultaneously available for a sample of individuals from the same population. The method proceeds by first identifying those markers whose variation across individuals is significantly correlated with individual phenotypic differences ("adaptive loci"). The proportion of phenotypic variance in the sample that is statistically accounted for by individual differences in adaptive loci is then estimated by fitting a linear model to the data, with trait value as the dependent variable and scores of adaptive loci as independent ones. The method can be easily extended to accommodate quantitative or qualitative information on biologically relevant features of the environment experienced by each sampled individual, in which case estimates of the environmental and genotype × environment components of phenotypic variance can also be obtained.

A twin study of erectile dysfunction.

PubMed

Fischer, Mary E; Vitek, Mary Ellen; Hedeker, Don; Henderson, William G; Jacobsen, Steven J; Goldberg, Jack

2004-01-26

The extent of genetic influence on erectile dysfunction (ED) is unknown. This study determines the contribution of heredity to ED in a sample of middle-aged men. A classical twin study was conducted in the Vietnam Era Twin Registry, a national sample of male-male pairs (mean birth year, 1949) who served on active duty during the Vietnam era (1965-1975). A 1999 male health survey was completed by 890 monozygotic (MZ) and 619 dizygotic (DZ) pairs. The prevalence and heritability of 2 self-report indicators of ED, difficulty in having an erection and in maintaining an erection, are estimated. The prevalence of difficulty in having an erection is 23.3% and in maintaining an erection is 26.7%. Twin correlations for dysfunction in having an erection are 0.35 (95% confidence interval [CI], 0.28-0.41) in MZ and 0.17 (95% CI, 0.09-0.27) in DZ pairs. For dysfunction in maintaining an erection, the twin correlations in MZ and DZ pairs are 0.39 (95% CI, 0.32-0.45) and 0.18 (95% CI, 0.09-0.27), respectively. The estimated heritability of liability for dysfunction in having an erection is 35% and in maintaining an erection is 42%. The heritable influence on ED remained significant after adjustment for ED risk factors. The present study demonstrates an ED-specific genetic component that is independent of genetic influences from numerous ED risk factors. The results suggest that future molecular genetic studies to identify ED-related polymorphisms are warranted.

Heritabilities of Facial Measurements and Their Latent Factors in Korean Families

PubMed Central

Kim, Hyun-Jin; Im, Sun-Wha; Jargal, Ganchimeg; Lee, Siwoo; Yi, Jae-Hyuk; Park, Jeong-Yeon; Sung, Joohon; Cho, Sung-Il; Kim, Jong-Yeol; Kim, Jong-Il; Seo, Jeong-Sun

2013-01-01

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest (h2 = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups. PMID:23843774

Genomic heritabilities and genomic estimated breeding values for methane traits in Angus cattle.

PubMed

Hayes, B J; Donoghue, K A; Reich, C M; Mason, B A; Bird-Gardiner, T; Herd, R M; Arthur, P F

2016-03-01

Enteric methane emissions from beef cattle are a significant component of total greenhouse gas emissions from agriculture. The variation between beef cattle in methane emissions is partly genetic, whether measured as methane production, methane yield (methane production/DMI), or residual methane production (observed methane production - expected methane production), with heritabilities ranging from 0.19 to 0.29. This suggests methane emissions could be reduced by selection. Given the high cost of measuring methane production from individual beef cattle, genomic selection is the most feasible approach to achieve this reduction in emissions. We derived genomic EBV (GEBV) for methane traits from a reference set of 747 Angus animals phenotyped for methane traits and genotyped for 630,000 SNP. The accuracy of GEBV was tested in a validation set of 273 Angus animals phenotyped for the same traits. Accuracies of GEBV ranged from 0.29 ± 0.06 for methane yield and 0.35 ± 0.06 for residual methane production. Selection on GEBV using the genomic prediction equations derived here could reduce emissions for Angus cattle by roughly 5% over 10 yr.

MutS HOMOLOG1-Derived Epigenetic Breeding Potential in Tomato1[OPEN

PubMed Central

Kundariya, Hardik; Xu, Ying-Zhi; Sandhu, Ajay; Yu, Jiantao; Zhang, Mingfang

2015-01-01

Evidence is compelling in support of a naturally occurring epigenetic influence on phenotype expression in land plants, although discerning the epigenetic contribution is difficult. Agriculturally important attributes like heterosis, inbreeding depression, phenotypic plasticity, and environmental stress response are thought to have significant epigenetic components, but unequivocal demonstration of this is often infeasible. Here, we investigate gene silencing of a single nuclear gene, MutS HOMOLOG1 (MSH1), in the tomato (Solanum lycopersicum) ‘Rutgers’ to effect developmental reprogramming of the plant. The condition is heritable in subsequent generations independent of the MSH1-RNA interference transgene. Crossing these transgene-null, developmentally altered plants to the isogenic cv Rutgers wild type results in progeny lines that show enhanced, heritable growth vigor under both greenhouse and field conditions. This boosted vigor appears to be graft transmissible and is partially reversed by treatment with the methylation inhibitor 5-azacytidine, implying the influence of mobile, epigenetic factors and DNA methylation changes. These data provide compelling evidence for the feasibility of epigenetic breeding in a crop plant. PMID:25736208

Independence of heritable influences on the food intake of free-living humans.

PubMed

de Castro, John M

2002-01-01

The time of day of meal ingestion, the number of people present at the meal, the subjective state of hunger, and the estimated before-meal contents in the stomach have been established as influences on the amount eaten in a meal and these influences have been shown to be heritable. Because these factors intercorrelate, the calculated heritabilities for some of these variables might result indirectly from their covariation with one of the other heritable variables. The independence of the heritability of the influence of these four factors was investigated with 110 identical and 102 fraternal same-sex and 53 fraternal mixed-sex adult twin pairs who were paid to maintain 7-d food-intake diaries. From the diary reports, the meal sizes were calculated and subjected to multiple regression analysis using the estimated before-meal stomach contents, the reported number of other people present, the subjective hunger ratings, and the time of day of the meal as predictors. Linear structural modeling was applied to the beta-coefficients from the multiple regression to investigate whether the heritability of the influences of these four variables was independent. Significant genetic effects were found for the beta-coefficients for all four variables, indicating that the heritability of their relationship with intake is to some extent independent and heritable. This suggests that influences of multiple factors on intake are influenced by the genes and become part of the total package of genetically determined physiologic, sociocultural, and psychological processes that regulate energy balance.

Heritability of diurnal changes in food intake in free-living humans.

PubMed

de Castro, J M

2001-09-01

The time of day of meal ingestion, the number of people present at the meal, the subjective state of hunger, and the estimated before-meal contents in the stomach have been established as influences on the amount eaten in a meal, and this influence has been shown to be heritable. Because these factors intercorrelate, the possibility that the calculated heritabilities for some of these variables could result indirectly from their convariation with one of the other heritable variables was assessed. The independence of the heritability of the influence of these four factors was investigated with 110 identical and 102 fraternal same-sex and 53 fraternal mixed-sex adult twin pairs who were paid to maintain 7-d food intake diaries. From the diary reports, the meal sizes were calculated and subjected to multiple regression analysis using the estimated before-meal stomach contents, the reported number of other people present, the subjective hunger ratings, and the time of day of the meal as predictors. Linear structural modeling was applied to the beta coefficients from the multiple regression to investigate whether the heritability of the influences of these four variables was independent. Significant genetic effects were found for the beta coefficients for all four variables, indicating that the heritability of their relationship with intake is to some extent heritable. These results suggest that the influences of multiple factors on intake are influenced by the genes and become part of the total package of genetically determined physiologic, sociocultural, and psychological processes that regulate energy balance.

Genetic Factors Influence Serological Measures of Common Infections

PubMed Central

Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.

2011-01-01

Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708

'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

PubMed

Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

2013-12-01

The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Parental Divorce and Disordered Eating: An Investigation of a Gene-Environment Interaction

PubMed Central

Suisman, Jessica Lynn; Burt, S. Alexandra; McGue, Matt; Iacono, William G.; Klump, Kelly L.

2010-01-01

Objective We investigated gene-environment interactions (G×E) for associations between parental divorce and disordered eating (DE). Method Participants were 1,810 female twins from the Michigan State University Twin Registry and the Minnesota Twin Family Study. The Minnesota Eating Behaviors Survey was used to assess DE. We tested for G×E by comparing the heritability of DE in twins from divorced versus intact families. It was hypothesized that divorce would moderate the heritability of DE, in that heritability would be higher in twins from divorced than twins from intact families. Results As expected, the heritability of body dissatisfaction was significantly higher in twins from divorced than intact families. However, genetic influences were equal in twins from divorced and intact families for all other forms of DE. Discussion Although divorce did not moderate heritability of most DE symptoms, future research should replicate G×Es for body dissatisfaction and identify factors underlying this unique relationship. PMID:21312202

Parental divorce and disordered eating: an investigation of a gene-environment interaction.

PubMed

Suisman, Jessica L; Burt, S Alexandra; McGue, Matt; Iacono, William G; Klump, Kelly L

2011-03-01

We investigated gene-environment interactions (GxE) for associations between parental divorce and disordered eating (DE). Participants were 1,810 female twins from the Michigan State University Twin Registry and the Minnesota Twin Family Study. The Minnesota Eating Behaviors Survey was used to assess DE. We tested for GxE by comparing the heritability of DE in twins from divorced versus intact families. It was hypothesized that divorce would moderate the heritability of DE, in that heritability would be higher in twins from divorced than twins from intact families. As expected, the heritability of body dissatisfaction was significantly higher in twins from divorced than intact families. However, genetic influences were equal in twins from divorced and intact families for all other forms of DE. Although divorce did not moderate heritability of most DE symptoms, future research should replicate GxEs for body dissatisfaction and identify factors underlying this unique relationship. Copyright © 2010 Wiley Periodicals, Inc.

Most genetic risk for autism resides with common variation

PubMed Central

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J.; Bodea, Corneliu A.; Goldberg, Arthur P.; Lee, Ann B.; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M.; Devlin, Bernie

2014-01-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation. PMID:25038753

Most genetic risk for autism resides with common variation.

PubMed

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J; Bodea, Corneliu A; Goldberg, Arthur P; Lee, Ann B; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M; Devlin, Bernie; Roeder, Kathryn; Buxbaum, Joseph D

2014-08-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.

Heritability and genetic integration of tooth size in the South Carolina Gullah.

PubMed

Stojanowski, Christopher M; Paul, Kathleen S; Seidel, Andrew C; Duncan, William N; Guatelli-Steinberg, Debbie

2017-11-01

This article provides estimates of narrow-sense heritability and genetic pleiotropy for mesiodistal tooth dimensions for a sample of 20th century African American individuals. Results inform biological distance analysis and offer insights into patterns of integration in the human dentition. Maximum mesiodistal crown dimensions were measured using Hillson-FitzGerald calipers on 469 stone dental casts from the Menegaz-Bock Collection. Narrow-sense heritability estimates and genetic and phenotypic correlations were estimated using SOLAR 8.1.1 with covariate screening for age, sex, age*sex interaction, and birth year. Heritability estimates were moderate (∼0.10 - 0.90; h 2 mean = 0.51) for most measured variables with sex as the only significant covariate. Patterns of genetic correlation indicate strong integration across tooth classes, except molars. Comparison of these results to previously published work suggests lower overall heritability relative to other human populations and much stronger genetic integration across tooth classes than obtained from nonhuman primate genetic pleiotropy estimates. These results suggest that the high heritabilities previously published may reflect overestimates inherent in previous study designs; as such the standard estimate of 0.55 used in biodistance analyses may not be appropriate. For the Gullah, isolation and endogamy coupled with elevated levels of physiological and economic stress may suppress narrow-sense heritability estimates. Pleiotropy analyses suggest a more highly integrated dentition in humans than in other mammals. © 2017 Wiley Periodicals, Inc.

Conditions that impact artificial hybridization of Arachis hypogaea L.

USDA-ARS?s Scientific Manuscript database

Modern farming is dependent on continual development of improved cultivars and efficient cultural management practices. In addition, dissecting genetic components of heritable traits also relies on the development of large mapping populations. Artificial hybridization is the critical initial step ...

Common heritable effects underpin concerns over norm maintenance and in-group favoritism: evidence from genetic analyses of right-wing authoritarianism and traditionalism.

PubMed

Lewis, Gary J; Bates, Timothy C

2014-08-01

Research has shown that in-group favoritism is associated with concerns over the maintenance of social norms. Here we present two studies examining whether genetic factors underpin this association. A classical twin design was used to decompose phenotypic variance into genetic and environmental components in two studies. Study 1 used 812 pairs of adult U.S. twins from the nationally representative MIDUS II sample. Study 2 used 707 pairs of middle-age twins from the Minnesota Twin Registry. In-group favoritism was measured with scales tapping preferences for in-group (vs. out-group) individuals; norm concerns were measured with the Multidimensional Personality Questionnaire-Traditionalism (Study 1) and Right-Wing Authoritarianism (RWA; Study 2) scales. In Study 1, heritable effects underlying traditionalism were moderately (c. 35%) overlapping with the genetic variance underpinning in-group favoritism. In Study 2, heritable influences on RWA were entirely shared with the heritable effects on in-group favoritism. Moreover, we observed that Big Five Openness shared common genetic links to both RWA and in-group favoritism. These results suggest that, at the genetic level, in-group favoritism is linked with a system related to concern over normative social practices, which is, in turn, partially associated with trait Openness. © 2013 Wiley Periodicals, Inc.

An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population

PubMed Central

Jenkins, Brittany R.; Vitousek, Maren N.; Hubbard, Joanna K.; Safran, Rebecca J.

2014-01-01

Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (Hirundo rustica erythrogaster). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns. PMID:25056627

The influence of heritability, neuroticism, maternal warmth and media use on disordered eating behaviors: a prospective analysis of twins.

PubMed

Ferguson, Christopher J; Muñoz, Monica E; Winegard, Ben; Winegard, Bo

2012-09-01

The relative impact of genetic and social influences on disordered eating behaviors (DEB) including binging, purging, excessive dieting and negative self-evaluations about weight remain an issue of debate. The current study sought to examine the relative influence of genetic and social influences on DEB. A 7-year prospective analysis of 580 monozygotic (MZ) and dizygotic (DZ) twins was conducted. Estimates of heritability of DEB were obtained using the DF Analysis Model. Regression equations revealed the relative predictive value of sibling's DEB, neurotic personality, maternal warmth and television and video game exposure on DEB. Heritability estimates for DEB were 0.40 for females and 0.48 for males. Among MZ and DZ twin pairs, female sex, neurotic personality and a genetic variable component, but not maternal warmth or school related problems, predicted DEB. Contrary to the expectations of media effects theory, greater media use was associated with lower DEB among DZ twins and had no influence on MZ twins. These results indicate that DEB is highly heritable and that personality variables may play an important role in the formation of DEB. This suggests that it is important to control for genetic variables when analyzing risk factors for DEB.

Gating Deficits are More Heritable and Correlate with Increased Clinical Severity in Schizophrenia Patients with a Positive versus Negative Family History

PubMed Central

Greenwood, Tiffany A.; Light, Gregory A.; Swerdlow, Neal R.; Calkins, Monica E.; Green, Michael F.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Freedman, Robert; Braff, David L.

2016-01-01

Objective The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here we investigated whether gating measures were more heritable in multiply affected families with a positive family history vs. families with only a single affected proband (singleton). Method A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Results Both PPI and P50 gating displayed significantly increased heritability in the 97 multiply affected families (47% and 36%, respectively), compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those derived from singleton families. Conclusions PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, which provides further support for the commonality of genes underlying both schizophrenia and gating measures. PMID:26441157

Random Regression Models Using Legendre Polynomials to Estimate Genetic Parameters for Test-day Milk Protein Yields in Iranian Holstein Dairy Cattle.

PubMed

Naserkheil, Masoumeh; Miraie-Ashtiani, Seyed Reza; Nejati-Javaremi, Ardeshir; Son, Jihyun; Lee, Deukhwan

2016-12-01

The objective of this study was to estimate the genetic parameters of milk protein yields in Iranian Holstein dairy cattle. A total of 1,112,082 test-day milk protein yield records of 167,269 first lactation Holstein cows, calved from 1990 to 2010, were analyzed. Estimates of the variance components, heritability, and genetic correlations for milk protein yields were obtained using a random regression test-day model. Milking times, herd, age of recording, year, and month of recording were included as fixed effects in the model. Additive genetic and permanent environmental random effects for the lactation curve were taken into account by applying orthogonal Legendre polynomials of the fourth order in the model. The lowest and highest additive genetic variances were estimated at the beginning and end of lactation, respectively. Permanent environmental variance was higher at both extremes. Residual variance was lowest at the middle of the lactation and contrarily, heritability increased during this period. Maximum heritability was found during the 12th lactation stage (0.213±0.007). Genetic, permanent, and phenotypic correlations among test-days decreased as the interval between consecutive test-days increased. A relatively large data set was used in this study; therefore, the estimated (co)variance components for random regression coefficients could be used for national genetic evaluation of dairy cattle in Iran.

Random Regression Models Using Legendre Polynomials to Estimate Genetic Parameters for Test-day Milk Protein Yields in Iranian Holstein Dairy Cattle

PubMed Central

Naserkheil, Masoumeh; Miraie-Ashtiani, Seyed Reza; Nejati-Javaremi, Ardeshir; Son, Jihyun; Lee, Deukhwan

2016-01-01

The objective of this study was to estimate the genetic parameters of milk protein yields in Iranian Holstein dairy cattle. A total of 1,112,082 test-day milk protein yield records of 167,269 first lactation Holstein cows, calved from 1990 to 2010, were analyzed. Estimates of the variance components, heritability, and genetic correlations for milk protein yields were obtained using a random regression test-day model. Milking times, herd, age of recording, year, and month of recording were included as fixed effects in the model. Additive genetic and permanent environmental random effects for the lactation curve were taken into account by applying orthogonal Legendre polynomials of the fourth order in the model. The lowest and highest additive genetic variances were estimated at the beginning and end of lactation, respectively. Permanent environmental variance was higher at both extremes. Residual variance was lowest at the middle of the lactation and contrarily, heritability increased during this period. Maximum heritability was found during the 12th lactation stage (0.213±0.007). Genetic, permanent, and phenotypic correlations among test-days decreased as the interval between consecutive test-days increased. A relatively large data set was used in this study; therefore, the estimated (co)variance components for random regression coefficients could be used for national genetic evaluation of dairy cattle in Iran. PMID:26954192

Breeding maize as biogas substrate in Central Europe: I. Quantitative-genetic parameters for testcross performance.

PubMed

Grieder, Christoph; Dhillon, Baldev S; Schipprack, Wolfgang; Melchinger, Albrecht E

2012-04-01

Biofuels have gained importance recently and the use of maize biomass as substrate in biogas plants for production of methane has increased tremendously in Germany. The objectives of our research were to (1) estimate variance components and heritability for different traits relevant to biogas production in testcrosses (TCs) of maize, (2) study correlations among traits, and (3) discuss strategies to breed maize as a substrate for biogas fermenters. We evaluated 570 TCs of 285 diverse dent maize lines crossed with two flint single-cross testers in six environments. Data were recorded on agronomic and quality traits, including dry matter yield (DMY), methane fermentation yield (MFY), and methane yield (MY), the product of DMY and MFY, as the main target trait. Estimates of variance components showed general combining ability (GCA) to be the major source of variation. Estimates of heritability exceeded 0.67 for all traits and were even much greater in most instances. Methane yield was perfectly correlated with DMY but not with MFY, indicating that variation in MY is primarily determined by DMY. Further, DMY had a larger heritability and coefficient of genetic variation than MFY. Hence, for improving MY, selection should primarily focus on DMY rather than MFY. Further, maize breeding for biogas production may diverge from that for forage production because in the former case, quality traits seem to be of much lower importance.

Measuring missing heritability: Inferring the contribution of common variants

PubMed Central

Golan, David; Lander, Eric S.; Rosset, Saharon

2014-01-01

Genome-wide association studies (GWASs), also called common variant association studies (CVASs), have uncovered thousands of genetic variants associated with hundreds of diseases. However, the variants that reach statistical significance typically explain only a small fraction of the heritability. One explanation for the “missing heritability” is that there are many additional disease-associated common variants whose effects are too small to detect with current sample sizes. It therefore is useful to have methods to quantify the heritability due to common variation, without having to identify all causal variants. Recent studies applied restricted maximum likelihood (REML) estimation to case–control studies for diseases. Here, we show that REML considerably underestimates the fraction of heritability due to common variation in this setting. The degree of underestimation increases with the rarity of disease, the heritability of the disease, and the size of the sample. Instead, we develop a general framework for heritability estimation, called phenotype correlation–genotype correlation (PCGC) regression, which generalizes the well-known Haseman–Elston regression method. We show that PCGC regression yields unbiased estimates. Applying PCGC regression to six diseases, we estimate the proportion of the phenotypic variance due to common variants to range from 25% to 56% and the proportion of heritability due to common variants from 41% to 68% (mean 60%). These results suggest that common variants may explain at least half the heritability for many diseases. PCGC regression also is readily applicable to other settings, including analyzing extreme-phenotype studies and adjusting for covariates such as sex, age, and population structure. PMID:25422463

Heritable victimization and the benefits of agonistic relationships

PubMed Central

Lea, Amanda J.; Blumstein, Daniel T.; Wey, Tina W.; Martin, Julien G. A.

2010-01-01

Here, we present estimates of heritability and selection on network traits in a single population, allowing us to address the evolutionary potential of social behavior and the poorly understood link between sociality and fitness. To evolve, sociality must have some heritable basis, yet the heritability of social relationships is largely unknown. Recent advances in both social network analyses and quantitative genetics allow us to quantify attributes of social relationships and estimate their heritability in free-living populations. Our analyses addressed a variety of measures (in-degree, out-degree, attractiveness, expansiveness, embeddedness, and betweenness), and we hypothesized that traits reflecting relationships controlled by an individual (i.e., those that the individual initiated or were directly involved in) would be more heritable than those based largely on the behavior of conspecifics. Identifying patterns of heritability and selection among related traits may provide insight into which types of relationships are important in animal societies. As expected, we found that variation in indirect measures was largely explained by nongenetic variation. Yet, surprisingly, traits capturing initiated interactions do not possess significant additive genetic variation, whereas measures of received interactions are heritable. Measures describing initiated aggression and position in an agonistic network are under selection (0.3 < |S| < 0.4), although advantageous trait values are not inherited by offspring. It appears that agonistic relationships positively influence fitness and seemingly costly or harmful ties may, in fact, be beneficial. Our study highlights the importance of studying agonistic as well as affiliative relationships to understand fully the connections between sociality and fitness. PMID:21115836

Heritability of hoarding symptoms across adolescence and young adulthood: A longitudinal twin study.

PubMed

Ivanov, Volen Z; Nordsletten, Ashley; Mataix-Cols, David; Serlachius, Eva; Lichtenstein, Paul; Lundström, Sebastian; Magnusson, Patrik K E; Kuja-Halkola, Ralf; Rück, Christian

2017-01-01

Twin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence. Univariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20-28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701). Heritability estimates for hoarding symptoms at ages 15, 18 and 20-28 were 41% (95% confidence interval [CI]: 36-45%), 31% (95% CI: 22-39%) and 29% (95% CI: 24-34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22-41%) and 17% (95% CI: 0-36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6-36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36-0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57-0.94). The bivariate heritability was estimated to 65% (95% CI: 50-79%). Hoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span.

Heritability of usual alcohol intoxication and hangover in male twins: the NAS-NRC Twin Registry.

PubMed

Wu, Sheng-Hui; Guo, Qin; Viken, Richard J; Reed, Terry; Dai, Jun

2014-08-01

Alcohol consumption is influenced by heritable factors. The genetic influence on usual high-density drinking, including alcohol intoxication and hangover, is unknown. We aim to estimate the heritability of usual high-density drinking. A total of 13,511 male twins in this cross-sectional study were included from the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry. Data on the frequency of alcohol intoxication and alcohol hangover over the past year, that is, usual high-density drinking (phenotypes), were collected through a self-administered questionnaire when twins were middle-aged in 1972. Structural equation modeling was used to estimate the variance components of phenotypes. The mean of the frequency of usual high-density drinking in the entire twin population was 0.16 times per month for intoxication and 0.18 times per month for hangover. The heritability of usual alcohol intoxication was 50.7% (95% confidence interval [CI] 46.2 to 55.0) before and 49.9% (95% CI 45.3 to 54.2) after the body mass index (BMI) adjustment. The heritability of usual hangover was 55.4% (95% CI 51.2 to 58.6) before and 54.8% (95% CI 50.6 to 58.8) after adjustment for BMI. Unshared environmental factors between co-twins explained the remaining variance in alcohol intoxication and in hangover. Both genetic and unshared environmental factors have important influences on usual alcohol intoxication and hangover. These findings are important in understanding the occurrence of and developing interventions for usual high-density drinking. Copyright © 2014 by the Research Society on Alcoholism.

Genetic and non-genetic correlates of vitamins K and D.

PubMed

Shea, M K; Benjamin, E J; Dupuis, J; Massaro, J M; Jacques, P F; D'Agostino, R B; Ordovas, J M; O'Donnell, C J; Dawson-Hughes, B; Vasan, R S; Booth, S L

2009-04-01

To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women. A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

The Genetic Architecture of Major Depressive Disorder in Han Chinese Women.

PubMed

Peterson, Roseann E; Cai, Na; Bigdeli, Tim B; Li, Yihan; Reimers, Mark; Nikulova, Anna; Webb, Bradley T; Bacanu, Silviu-Alin; Riley, Brien P; Flint, Jonathan; Kendler, Kenneth S

2017-02-01

Despite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD. To apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants. The CONVERGE (China, Oxford, and Virginia Commonwealth University Experimental Research on Genetic Epidemiology) study collected data on 5278 patients with recurrent MDD from 58 provincial mental health centers and psychiatric departments of general medical hospitals in 45 cities and 23 provinces of China. Screened controls (n = 5196) were recruited from a range of locations, including general hospitals and local community centers. Data were collected from August 1, 2008, to October 31, 2012. Genetic risk for liability to recurrent MDD was partitioned using sparse whole-genome sequencing. In aggregate, common single-nucleotide polymorphisms (SNPs) explained between 20% and 29% of the variance in MDD risk, and the heritability in MDD explained by each chromosome was proportional to its length (r = 0.680; P = .0003), supporting a common polygenic etiology. Partitioning heritability by minor allele frequency indicated that the variance explained was distributed across the allelic frequency spectrum, although relatively common SNPs accounted for a disproportionate fraction of risk. Partitioning by genic annotation indicated a greater contribution of SNPs in protein-coding regions and within 3'-UTR regions of genes. Enrichment of SNPs associated with DNase I-hypersensitive sites was also found in many tissue types, including brain tissue. Examining burden scores from singleton exonic SNPs predicted to be deleterious indicated that cases had significantly more mutations than controls (odds ratio, 1.009; 95% CI, 1.003-1.014; P = .003), including those occurring in genes expressed in the brain (odds ratio, 1.011; 95% CI, 1.003-1.018; P = .004) and within nuclear-encoded genes with mitochondrial gene products (odds ratio, 1.075; 95% CI, 1.018-1.135; P = .009). Results support a complex etiology for MDD and highlight the value of analyzing components of heritability to clarify genetic architecture.

The Genetic Architecture of Major Depressive Disorder in Han Chinese Women

PubMed Central

Peterson, Roseann E.; Cai, Na; Bigdeli, Tim B.; Li, Yihan; Reimers, Mark; Nikulova, Anna; Webb, Bradley T.; Bacanu, Silviu-Alin; Riley, Brien P.; Flint, Jonathan; Kendler, Kenneth S.

2017-01-01

IMPORTANCE Despite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD. OBJECTIVES To apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants. DESIGN, SETTING, AND PARTICIPANTS The CONVERGE (China, Oxford, and Virginia Commonwealth University Experimental Research on Genetic Epidemiology) study collected data on 5278 patients with recurrent MDD from 58 provincial mental health centers and psychiatric departments of general medical hospitals in 45 cities and 23 provinces of China. Screened controls (n = 5196) were recruited from a range of locations, including general hospitals and local community centers. Data were collected from August 1, 2008, to October 31, 2012. MAIN OUTCOMES AND MEASURES Genetic risk for liability to recurrent MDD was partitioned using sparse whole-genome sequencing. RESULTS In aggregate, common single-nucleotide polymorphisms (SNPs) explained between 20% and 29% of the variance in MDD risk, and the heritability in MDD explained by each chromosome was proportional to its length (r = 0.680; P = .0003), supporting a common polygenic etiology. Partitioning heritability by minor allele frequency indicated that the variance explained was distributed across the allelic frequency spectrum, although relatively common SNPs accounted for a disproportionate fraction of risk. Partitioning by genic annotation indicated a greater contribution of SNPs in protein-coding regions and within 3′-UTR regions of genes. Enrichment of SNPs associated with DNase I-hypersensitive sites was also found in many tissue types, including brain tissue. Examining burden scores from singleton exonic SNPs predicted to be deleterious indicated that cases had significantly more mutations than controls (odds ratio, 1.009; 95% CI, 1.003–1.014; P = .003), including those occurring in genes expressed in the brain (odds ratio, 1.011; 95% CI, 1.003–1.018; P = .004) and within nuclear-encoded genes with mitochondrial gene products (odds ratio, 1.075; 95% CI, 1.018–1.135; P = .009). CONCLUSIONS AND RELEVANCE Results support a complex etiology for MDD and highlight the value of analyzing components of heritability to clarify genetic architecture. PMID:28002544

Familial aggregation of circulating C-reactive protein in polycystic ovary syndrome.

PubMed

Sasidevi, Arunachalam; Vellanki, Priyathama; Kunselman, Allen R; Raja-Khan, Nazia; Dunaif, Andrea; Legro, Richard S

2013-03-01

What is the heritability of C-reactive protein (CRP) levels in women with polycystic ovary syndrome (PCOS) and their first-degree relatives? Women with PCOS and their siblings are more likely to have elevated CRP levels when both of their parents have elevated CRP. This PCOS family-based study indicates that CRP levels are likely a heritable trait. Previous studies have established that an elevated blood level of CRP is variably present in women with PCOS, and may be present independent of metabolic status. A familial based phenotyping study consisting of 81 families comprised of PCOS patients and their first-degree relatives for 305 subjects. Study conducted at an academic health center. An elevated CRP level was defined as >28.6 nmol/l. To account for familial clustering, generalized estimating equations with a logit link were used to model the association between elevated CRP levels in patients with PCOS and their siblings with their parental group (A = neither parent with elevated CRP; B = one parent with elevated CRP; C= both parents with elevated CRP), adjusting for gender, age and BMI of the offspring. We did additional heritability analyses by using a variance component estimation method for CRP levels, adjusting for sex, age and BMI. We observed elevated CRP levels in 94% of the offspring in group C, 45% in group B and 10% in group A after adjusting for age, gender and BMI of the offspring. The median BMI of the offspring in group A, B and C were 30.0, 28.7 and 31.2 kg/m², respectively. Heritability estimates of CRP levels ranged from 0.75 to 0.83 and remained significant after excluding for type 2 diabetes mellitus. Our small sample size increases the possibility of a type 1 error. This is a single report in an adequately powered but limited sample size study identifying the strong heritability of CRP levels. Replication in other large family cohorts is necessary. These findings support the concept that there is an increased cardiovascular disease risk profile in families of women with PCOS. This research was supported by National Institutes of Health grants U54HD-034449 and P50 HD044405 (A.D.). Priyathama Vellanki is supported in part by NIH/NIDDK Training Grant T32 DK007169.

Environmental quality and evolutionary potential: lessons from wild populations

PubMed Central

Charmantier, Anne; Garant, Dany

2005-01-01

An essential requirement to determine a population's potential for evolutionary change is to quantify the amount of genetic variability expressed for traits under selection. Early investigations in laboratory conditions showed that the magnitude of the genetic and environmental components of phenotypic variation can change with environmental conditions. However, there is no consensus as to how the expression of genetic variation is sensitive to different environmental conditions. Recently, the study of quantitative genetics in the wild has been revitalized by new pedigree analyses based on restricted maximum likelihood, resulting in a number of studies investigating these questions in wild populations. Experimental manipulation of environmental quality in the wild, as well as the use of naturally occurring favourable or stressful environments, has broadened the treatment of different taxa and traits. Here, we conduct a meta-analysis on recent studies comparing heritability in favourable versus unfavourable conditions in non-domestic and non-laboratory animals. The results provide evidence for increased heritability in more favourable conditions, significantly so for morphometric traits but not for traits more closely related to fitness. We discuss how these results are explained by underlying changes in variance components, and how they represent a major step in our understanding of evolutionary processes in wild populations. We also show how these trends contrast with the prevailing view resulting mainly from laboratory experiments on Drosophila. Finally, we underline the importance of taking into account the environmental variation in models predicting quantitative trait evolution. PMID:16011915

Sleep reactivity and insomnia: genetic and environmental influences.

PubMed

Drake, Christopher L; Friedman, Naomi P; Wright, Kenneth P; Roth, Thomas

2011-09-01

Determine the genetic and environmental contributions to sleep reactivity and insomnia. Population-based twin cohort. 1782 individual twins (988 monozygotic or MZ; 1,086 dizygotic or DZ), including 744 complete twin pairs (377 MZ and 367 DZ). Mean age was 22.5 ± 2.8 years; gender distribution was 59% women. Sleep reactivity was measured using the Ford Insomnia Response to Stress Test (FIRST). The criterion for insomnia was having difficulty falling asleep, staying asleep, or nonrefreshing sleep "usually or always" for ≥ 1 month, with at least "somewhat" interference with daily functioning. The prevalence of insomnia was 21%. Heritability estimates for sleep reactivity were 29% for females and 43% for males. The environmental variance for sleep reactivity was greater for females and entirely due to nonshared effects. Insomnia was 43% to 55% heritable for males and females, respectively; the sex difference was not significant. The genetic variances in insomnia and FIRST scores were correlated (r = 0.54 in females, r = 0.64 in males), as were the environmental variances (r = 0.32 in females, r = 0.37 in males). In terms of individual insomnia symptoms, difficulty staying asleep (25% to 35%) and nonrefreshing sleep (34% to 35%) showed relatively more genetic influences than difficulty falling asleep (0%). Sleep reactivity to stress has a substantial genetic component, as well as an environmental component. The finding that FIRST scores and insomnia symptoms share genetic influences is consistent with the hypothesis that sleep reactivity may be a genetic vulnerability for developing insomnia.

Additive-dominance genetic model analyses for late-maturity alpha-amylase activity in a bread wheat factorial crossing population.

PubMed

Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Ibrahim, Amir M H

2015-12-01

Elevated level of late maturity α-amylase activity (LMAA) can result in low falling number scores, reduced grain quality, and downgrade of wheat (Triticum aestivum L.) class. A mating population was developed by crossing parents with different levels of LMAA. The F2 and F3 hybrids and their parents were evaluated for LMAA, and data were analyzed using the R software package 'qgtools' integrated with an additive-dominance genetic model and a mixed linear model approach. Simulated results showed high testing powers for additive and additive × environment variances, and comparatively low powers for dominance and dominance × environment variances. All variance components and their proportions to the phenotypic variance for the parents and hybrids were significant except for the dominance × environment variance. The estimated narrow-sense heritability and broad-sense heritability for LMAA were 14 and 54%, respectively. High significant negative additive effects for parents suggest that spring wheat cultivars 'Lancer' and 'Chester' can serve as good general combiners, and that 'Kinsman' and 'Seri-82' had negative specific combining ability in some hybrids despite of their own significant positive additive effects, suggesting they can be used as parents to reduce LMAA levels. Seri-82 showed very good general combining ability effect when used as a male parent, indicating the importance of reciprocal effects. High significant negative dominance effects and high-parent heterosis for hybrids demonstrated that the specific hybrid combinations; Chester × Kinsman, 'Lerma52' × Lancer, Lerma52 × 'LoSprout' and 'Janz' × Seri-82 could be generated to produce cultivars with significantly reduced LMAA level.

Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases.

PubMed

George, Rani; Kovak, Karen; Cox, Summer L

2015-06-01

Cascade genetic screening is a methodology for identifying and testing close blood relatives of individuals at increased risk for heritable conditions and follows a sequential process, minimizing testing costs and the number of family members who need to be tested. It offers considerable potential for cost savings and increased awareness of heritable conditions within families. CDC-classified Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are recommended for clinical use and support the use of cascade genetic screening. Most individuals are unaware of their increased risk for heritable conditions such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening could significantly increase awareness and prevention of heritable conditions. Limitations to effective implementation of cascade genetic screening include: insufficient genetic risk assessment and knowledge by a majority of healthcare providers without genetics credentials; a shortage of genetic specialists, especially in rural areas; a low rate of reimbursement for comprehensive genetic counseling services; and an individual focus on prevention by clinical guidelines and insurance coverage. The family-centric approach of cascade genetic screening improves prevention and early diagnosis of heritable diseases on a population health level. Cascade genetic screening could be better supported and augmented through changes in health policy.

Heritability of Performance Deficit Accumulation During Acute Sleep Deprivation in Twins

PubMed Central

Kuna, Samuel T.; Maislin, Greg; Pack, Frances M.; Staley, Bethany; Hachadoorian, Robert; Coccaro, Emil F.; Pack, Allan I.

2012-01-01

Study Objectives: To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. Design: Prospective, observational cohort study. Setting: Academic medical center. Participants: There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. Interventions: Thirty-eight hr of monitored, continuous sleep deprivation. Measurements and Results: Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h2) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects. Conclusion: Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation. Citation: Kuna ST; Maislin G; Pack FM; Staley B; Hachadoorian R; Coccaro EF; Pack AI. Heritability of performance deficit accumulation during acute sleep deprivation in twins. SLEEP 2012;35(9):1223-1233. PMID:22942500

Determinants and Heritability of Intraocular Pressure and Cup-to-Disc Ratio in a Defined Older Population

PubMed Central

Chang, Ta C.; Congdon, Nathan G.; Wojciechowski, Robert; Muñoz, Beatriz; Gilbert, Donna; Chen, Ping; Friedman, David S.; West, Sheila K.

2011-01-01

Purpose To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population. Design Family-based cohort study. Participants Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships. Methods Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glacuoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP. Main Outcome Measures Heritability and determinants of IOP and CDR, and impact of siblings’ glaucoma status on IOP and CDR. Results We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12–0.46) for IOP and 0.56 (95% CI, 0.35–0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004). Conclusions In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands. PMID:15939473

Familiality and SNP heritability of age at onset and episodicity in major depressive disorder.

PubMed

Ferentinos, P; Koukounari, A; Power, R; Rivera, M; Uher, R; Craddock, N; Owen, M J; Korszun, A; Jones, L; Jones, I; Gill, M; Rice, J P; Ising, M; Maier, W; Mors, O; Rietschel, M; Preisig, M; Binder, E B; Aitchison, K J; Mendlewicz, J; Souery, D; Hauser, J; Henigsberg, N; Breen, G; Craig, I W; Farmer, A E; Müller-Myhsok, B; McGuffin, P; Lewis, C M

2015-07-01

Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Quantitative trait locus on chromosome 1q influences bone loss in young Mexican American adults

PubMed Central

Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

2009-01-01

Introduction Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants of the San Antonio Family Osteoporosis Study. Materials and Methods BMD change in 327 Mexican Americans (ages 25–45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h2) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm, and estimate heritability for BMD change of lumbar spine. Results BMD change was significantly heritable for total hip, ultradistal radius and 33% radius (h2 = 0.34, 0.34, 0.27, respectively, p < 0.03 for all), modestly heritable for femoral neck (h2 = 0.22, p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. Conclusions We observed that change in BMD in young adults is heritable, and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests this region may harbor one or more genes involved in regulating early BMD change of the femoral neck. PMID:19067020

The Heritability of Mating Behaviour in a Fly and Its Plasticity in Response to the Threat of Sperm Competition

PubMed Central

Bretman, Amanda; Lizé, Anne; Walling, Craig A.; Price, Tom A. R.

2014-01-01

Phenotypic plasticity is a key mechanism by which animals can cope with rapidly changeable environments, but the evolutionary lability of such plasticity remains unclear. The socio-sexual environment can fluctuate very rapidly, affecting both the frequency of mating opportunities and the level of competition males may face. Males of many species show plastic behavioural responses to changes in social environment, in particular the presence of rival males. For example, Drosophila pseudoobscura males respond to rivals by extending mating duration and increasing ejaculate size. Whilst such responses are predicted to be adaptive, the extent to which the magnitude of response is heritable, and hence selectable, is unknown. We investigated this using isofemale lines of the fruit fly D. pseudoobscura, estimating heritability of mating duration in males exposed or not to a rival, and any genetic basis to the change in this trait between these environments (i.e. degree of plasticity). The two populations differed in population sex ratio, and the presence of a sex ratio distorting selfish chromosome. We find that mating duration is heritable, but no evidence of population differences. We find no significant heritability of plasticity in mating duration in one population, but borderline significant heritability of plasticity in the second. This difference between populations might be related to the presence of the sex ratio distorting selfish gene in the latter population, but this will require investigation in additional populations to draw any conclusions. We suggest that there is scope for selection to produce an evolutionary response in the plasticity of mating duration in response to rivals in D. pseudoobscura, at least in some populations. PMID:24587294

The heritability of mating behaviour in a fly and its plasticity in response to the threat of sperm competition.

PubMed

Bretman, Amanda; Lizé, Anne; Walling, Craig A; Price, Tom A R

2014-01-01

Phenotypic plasticity is a key mechanism by which animals can cope with rapidly changeable environments, but the evolutionary lability of such plasticity remains unclear. The socio-sexual environment can fluctuate very rapidly, affecting both the frequency of mating opportunities and the level of competition males may face. Males of many species show plastic behavioural responses to changes in social environment, in particular the presence of rival males. For example, Drosophila pseudoobscura males respond to rivals by extending mating duration and increasing ejaculate size. Whilst such responses are predicted to be adaptive, the extent to which the magnitude of response is heritable, and hence selectable, is unknown. We investigated this using isofemale lines of the fruit fly D. pseudoobscura, estimating heritability of mating duration in males exposed or not to a rival, and any genetic basis to the change in this trait between these environments (i.e. degree of plasticity). The two populations differed in population sex ratio, and the presence of a sex ratio distorting selfish chromosome. We find that mating duration is heritable, but no evidence of population differences. We find no significant heritability of plasticity in mating duration in one population, but borderline significant heritability of plasticity in the second. This difference between populations might be related to the presence of the sex ratio distorting selfish gene in the latter population, but this will require investigation in additional populations to draw any conclusions. We suggest that there is scope for selection to produce an evolutionary response in the plasticity of mating duration in response to rivals in D. pseudoobscura, at least in some populations.

Intrafamilial aggregation and heritability of office-day blood pressure difference in a community of African ancestry: implications for genetic association studies.

PubMed

Djami-Tchatchou, Arnaud T; Norton, Gavin R; Redelinghuys, Michelle; Maseko, Muzi J; Majane, Olebogeng H I; Woodiwiss, Angela J

2014-12-01

An inability to show consistent relationships between gene variants and blood pressure (BP) may be confounded by the use of office BP measurement. Whether the difference between office BP and day BP (office-day) is genetically predetermined is unknown. We therefore aimed to determine the intrafamilial aggregation and heritability of office-day BP. Nurse-derived office BP (mean of 5 measurements according to guidelines) and 24-h ambulatory BP were determined for 592 participants from 198 families (67 spouse pairs, 361 parent-child pairs, and 169 sibling-sibling pairs), with 12 families having three generations, from an urban developing community of black Africans. Heritability estimates were determined using SAGE software. With adjustments for confounders, office systolic BP (SBP) (h=0.35±0.09, P<0.0001) showed comparable heritability estimates to 24-h SBP (h=0.33±0.09, P<0.0001). Similarly, with adjustments for confounders, office diastolic BP (DBP) (h=0.37±0.09, P<0.0001) showed comparable heritability estimates as 24-h DBP (h=0.35±0.09, P<0.0001). However, multivariate adjusted heritability estimates of day SBP (h=0.29±0.09, P<0.0001) and DBP (h=0.33±0.09, P<0.0001) were not diminished by further adjustments for office SBP (h=0.42±0.09, P<0.0001) or DBP (h=0.34±0.09, P<0.0001). Further, independent of confounders, office-day BP showed significant intrafamilial aggregation and heritability (SBP: h=0.51±0.10, P<0.0001; DBP: h=0.37±0.09, P<0.0001), effects that persisted with further adjustments for office, day, or day-night BP (P<0.0005 for SBP and DBP). Although office and ambulatory BP may show similar heritability estimates, genetic associations with carefully determined office BP measurements may be confounded by the heritability of office-day BP differences.

Mapping QTL influencing gastrointestinal nematode burden in Dutch Holstein-Friesian dairy cattle

PubMed Central

Coppieters, Wouter; Mes, Ted HM; Druet, Tom; Farnir, Frédéric; Tamma, Nico; Schrooten, Chris; Cornelissen, Albert WCA; Georges, Michel; Ploeger, Harm W

2009-01-01

Background Parasitic gastroenteritis caused by nematodes is only second to mastitis in terms of health costs to dairy farmers in developed countries. Sustainable control strategies complementing anthelmintics are desired, including selective breeding for enhanced resistance. Results and Conclusion To quantify and characterize the genetic contribution to variation in resistance to gastro-intestinal parasites, we measured the heritability of faecal egg and larval counts in the Dutch Holstein-Friesian dairy cattle population. The heritability of faecal egg counts ranged from 7 to 21% and was generally higher than for larval counts. We performed a whole genome scan in 12 paternal half-daughter groups for a total of 768 cows, corresponding to the ~10% most and least infected daughters within each family (selective genotyping). Two genome-wide significant QTL were identified in an across-family analysis, respectively on chromosomes 9 and 19, coinciding with previous findings in orthologous chromosomal regions in sheep. We identified six more suggestive QTL by within-family analysis. An additional 73 informative SNPs were genotyped on chromosome 19 and the ensuing high density map used in a variance component approach to simultaneously exploit linkage and linkage disequilibrium in an initial inconclusive attempt to refine the QTL map position. PMID:19254385

Socioeconomic Status (SES) and Children's Intelligence (IQ): In a UK-Representative Sample SES Moderates the Environmental, Not Genetic, Effect on IQ

PubMed Central

Hanscombe, Ken B.; Trzaskowski, Maciej; Haworth, Claire M. A.; Davis, Oliver S. P.; Dale, Philip S.; Plomin, Robert

2012-01-01

Background The environment can moderate the effect of genes - a phenomenon called gene-environment (GxE) interaction. Several studies have found that socioeconomic status (SES) modifies the heritability of children's intelligence. Among low-SES families, genetic factors have been reported to explain less of the variance in intelligence; the reverse is found for high-SES families. The evidence however is inconsistent. Other studies have reported an effect in the opposite direction (higher heritability in lower SES), or no moderation of the genetic effect on intelligence. Methods Using 8716 twin pairs from the Twins Early Development Study (TEDS), we attempted to replicate the reported moderating effect of SES on children's intelligence at ages 2, 3, 4, 7, 9, 10, 12 and 14: i.e., lower heritability in lower-SES families. We used a twin model that allowed for a main effect of SES on intelligence, as well as a moderating effect of SES on the genetic and environmental components of intelligence. Results We found greater variance in intelligence in low-SES families, but minimal evidence of GxE interaction across the eight ages. A power calculation indicated that a sample size of about 5000 twin pairs is required to detect moderation of the genetic component of intelligence as small as 0.25, with about 80% power - a difference of 11% to 53% in heritability, in low- (−2 standard deviations, SD) and high-SES (+2 SD) families. With samples at each age of about this size, the present study found no moderation of the genetic effect on intelligence. However, we found the greater variance in low-SES families is due to moderation of the environmental effect – an environment-environment interaction. Conclusions In a UK-representative sample, the genetic effect on intelligence is similar in low- and high-SES families. Children's shared experiences appear to explain the greater variation in intelligence in lower SES. PMID:22312423

Sexual Dimorphism in Melanin Pigmentation, Feather Coloration and Its Heritability in the Barn Swallow (Hirundo rustica)

PubMed Central

Saino, Nicola; Romano, Maria; Rubolini, Diego; Teplitsky, Celine; Ambrosini, Roberto; Caprioli, Manuela; Canova, Luca; Wakamatsu, Kazumasa

2013-01-01

Melanin is the main pigment in animal coloration and considerable variation in the concentrations of the two melanin forms (pheo- and eumlanin) in pigmented tissues exists among populations and individuals. Melanin-based coloration is receiving increasing attention particularly in socio-sexual communication contexts because the melanocortin system has been hypothesized to provide a mechanistic basis for covariation between coloration and fitness traits. However, with few notable exceptions, little detailed information is available on inter-individual and inter-population variation in melanin pigmentation and on its environmental, genetic and ontogenetic components. Here, we investigate melanin-based coloration in an Italian population of a passerine bird, the barn swallow (Hirundo rustica rustica), its sex- and age-related variation, and heritability. The concentrations of eu- and pheomelanin in the throat (brown) and belly (white-to-brownish) feathers differed between sexes but not according to age. The relative concentration of either melanin (Pheo:Eu) differed between sexes in throat but not in belly feathers, and the concentrations in males compared to females were larger in belly than in throat feathers. There were weak correlations between the concentrations of melanins within as well as among plumage regions. Coloration of belly feathers was predicted by the concentration of both melanins whereas coloration of throat feathers was only predicted by pheomelanin in females. In addition, Pheo:Eu predicted coloration of throat feathers in females and that of belly feathers in males. Finally, we found high heritability of color of throat feathers. Melanization was found to differ from that recorded in Hirundo rustica rustica from Scotland or from H. r. erythrogaster from North America. Hence, present results show that pigmentation strategies vary in a complex manner according to sex and plumage region, and also among geographical populations, potentially reflecting adaptation to different natural and sexual selection regimes, and that some coloration components seem to be highly heritable. PMID:23469134

Can metamorphosis survival during larval development in spiny lobster Sagmariasus verreauxi be improved through quantitative genetic inheritance?

PubMed

Nguyen, Nguyen H; Fitzgibbon, Quinn P; Quinn, Jane; Smith, Greg; Battaglene, Stephen; Knibb, Wayne

2018-05-04

One of the major impediments to spiny lobster aquaculture is the high cost of hatchery production due to the long and complex larval cycle and poor survival during the many moult stages, especially at metamorphosis. We examined if the key trait of larval survival can be improved through selection by determining if genetic variance exists for this trait. Specifically, we report, for the first time, genetic parameters (heritability and correlations) for early survival rates recorded at five larval phases; early-phyllosoma stages (instars 1-6; S1), mid-phyllosoma stages (instars; 7-12; S2), late-phyllosoma stages (instars 13-17; S3), metamorphosis (S4) and puerulus stage (S5) in hatchery-reared spiny lobster Sagmariasus verreauxi. The data were collected from a total of 235,060 larvae produced from 18 sires and 30 dams over nine years (2006 to 2014). Parentage of the offspring and full-sib families was verified using ten microsatellite markers. Analysis of variance components showed that the estimates of heritability for all the five phases of larval survival obtained from linear mixed model were generally similar to those obtained from threshold logistic generalised models (0.03-0.47 vs. 0.01-0.50). The heritability estimates for survival traits recorded in the early larval phases (S1 and S2) were higher than those estimated in later phases (S3, S4 and S5). The existence of the additive genetic component in larval survival traits indicate that they could be improved through selection. Both phenotypic and genetic correlations among the five survival measures studied were moderate to high and positive. The genetic associations between successive rearing periods were stronger than those that are further apart. Our estimates of heritability and genetic correlations reported here in a spiny lobster species indicate that improvement in the early survival especially during metamorphosis can be achieved through genetic selection in this highly economic value species.

Medial Demons Registration Localizes The Degree of Genetic Influence Over Subcortical Shape Variability: An N= 1480 Meta-Analysis

PubMed Central

Gutman, Boris A.; Jahanshad, Neda; Ching, Christopher R.K.; Wang, Yalin; Kochunov, Peter V.; Nichols, Thomas E.; Thompson, Paul M.

2015-01-01

We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens. Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies. PMID:26413211

Medial Demons Registration Localizes The Degree of Genetic Influence Over Subcortical Shape Variability: An N= 1480 Meta-Analysis.

PubMed

Gutman, Boris A; Jahanshad, Neda; Ching, Christopher R K; Wang, Yalin; Kochunov, Peter V; Nichols, Thomas E; Thompson, Paul M

2015-04-01

We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens . Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies.

Heritability of high reading ability and its interaction with parental education.

PubMed

Friend, Angela; DeFries, John C; Olson, Richard K; Pennington, Bruce; Harlaar, Nicole; Byrne, Brian; Samuelsson, Stefan; Willcutt, Erik G; Wadsworth, Sally J; Corley, Robin; Keenan, Janice M

2009-07-01

Moderation of the level of genetic influence on children's high reading ability by environmental influences associated with parental education was explored in two independent samples of identical and fraternal twins from the United States and Great Britain. For both samples, the heritability of high reading performance increased significantly with lower levels of parental education. Thus, resilience (high reading ability despite lower environmental support) is more strongly influenced by genotype than is high reading ability with higher environmental support. This result provides a coherent account when considered alongside results of previous research showing that heritability for low reading ability decreased with lower levels of parental education.

We are making inroads on health and fitness traits

USDA-ARS?s Scientific Manuscript database

Dairy producers have used genetic selection to make dramatic improvements in milk and components yields over the past 50 years. Production traits are easy to measure, have relatively high heritabilities, and are directly tied to the financial success of the farm enterprise. The increasing importance...

Estimation of genetic parameters and detection of quantitative trait loci for metabolites in Danish Holstein milk.

PubMed

Buitenhuis, A J; Sundekilde, U K; Poulsen, N A; Bertram, H C; Larsen, L B; Sørensen, P

2013-05-01

Small components and metabolites in milk are significant for the utilization of milk, not only in dairy food production but also as disease predictors in dairy cattle. This study focused on estimation of genetic parameters and detection of quantitative trait loci for metabolites in bovine milk. For this purpose, milk samples were collected in mid lactation from 371 Danish Holstein cows in first to third parity. A total of 31 metabolites were detected and identified in bovine milk by using (1)H nuclear magnetic resonance (NMR) spectroscopy. Cows were genotyped using a bovine high-density single nucleotide polymorphism (SNP) chip. Based on the SNP data, a genomic relationship matrix was calculated and used as a random factor in a model together with 2 fixed factors (herd and lactation stage) to estimate the heritability and breeding value for individual metabolites in the milk. Heritability was in the range of 0 for lactic acid to >0.8 for orotic acid and β-hydroxybutyrate. A single SNP association analysis revealed 7 genome-wide significant quantitative trait loci [malonate: Bos taurus autosome (BTA)2 and BTA7; galactose-1-phosphate: BTA2; cis-aconitate: BTA11; urea: BTA12; carnitine: BTA25; and glycerophosphocholine: BTA25]. These results demonstrate that selection for metabolites in bovine milk may be possible. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Heritability of cardiovascular risk factors in a Chinese population--Taichung Community Health Study and Family Cohort.

PubMed

Lin, Cheng-Chieh; Peyser, Patricia A; Kardia, Sharon L R; Li, Chia-Ing; Liu, Chiu-Shong; Chu, Julia S; Lin, Wen-Yuan; Li, Tsai-Chung

2014-08-01

Previous studies reporting on estimates of heritability of cardiovascular risk factors in Chinese are limited. This study aims to estimate the heritability of cardiovascular risk factors in relatives of residents who participated in the Taichung Community Health Study (TCHS) and Family Cohort (TCHS-FC) while controlling as many potential confounders as possible. A total of 1564 study subjects from 494 families with members aged 12-91 years were enrolled from a random sample of participants of TCHS and their family members (TCHS-FC) from 2009 to 2012. Anthropometric measurement, body composition, blood pressure, plasma lipids, fasting glucose, insulin, highly sensitive C-reactive protein (hs-CRP), brachial-ankle pulse wave velocity (baPWV), and the ankle-brachial index (ABI), as well as a questionnaire interview, were obtained from each participant. Cardiovascular risk factors with estimates of heritability greater than 30% after multivariate adjustment were triglyceride (h(2) = 0.41), HDL-C (h(2) = 0.49), LDL-C (h(2) = 0.47), total cholesterol (h(2) = 0.46), hip circumference (h(2) = 0.44), weight (h(2) = 0.42), insulin (h(2) = 0.39), hs-CRP (h(2) = 0.38), BMI (h(2) = 0.38), and percent body fat mass (h(2) = 0.35). Correlation coefficients for significant sibling varied from 0.10 for weight to 0.47 for LDL-C whereas those for significant parent-offspring varied from 0.09 for fasting plasma glucose to 0.43 for baPWV. This study demonstrated significant heritability and familial aggregation of cardiovascular risk factors in a random sample of ethnic Chinese population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Heritability, linkage, and genetic associations of exercise treadmill test responses.

PubMed

Ingelsson, Erik; Larson, Martin G; Vasan, Ramachandran S; O'Donnell, Christopher J; Yin, Xiaoyan; Hirschhorn, Joel N; Newton-Cheh, Christopher; Drake, Jared A; Musone, Stacey L; Heard-Costa, Nancy L; Benjamin, Emelia J; Levy, Daniel; Atwood, Larry D; Wang, Thomas J; Kathiresan, Sekar

2007-06-12

The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43-44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing. Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.

Repeatability and heritability of reproductive traits in free-ranging snakes.

PubMed

Brown, G P; Shine, R

2007-03-01

The underlying genetic basis of life-history traits in free-ranging animals is critical to the effects of selection on such traits, but logistical constraints mean that such data are rarely available. Our long-term ecological studies on free-ranging oviparous snakes (keelbacks, Tropidonophis mairii (Gray, 1841), Colubridae) on an Australian floodplain provide the first such data for any tropical reptile. All size-corrected reproductive traits (egg mass, clutch size, clutch mass and post-partum maternal mass) were moderately repeatable between pairs of clutches produced by 69 female snakes after intervals of 49-1152 days, perhaps because maternal body condition was similar between clutches. Parent-offspring regression of reproductive traits of 59 pairs of mothers and daughters revealed high heritability for egg mass (h2= 0.73, SE=0.24), whereas heritability for the other three traits was low (< 0.37). The estimated heritability of egg mass may be inflated by maternal effects such as differential allocation of yolk steroids to different-sized eggs. High heritability of egg size may be maintained (rather than eroded by stabilizing selection) because selection acts on a trait (hatchling size) that is determined by the interaction between egg size and incubation substrate rather than by egg size alone. Variation in clutch size was mainly because of environmental factors (h2=0.04), indicating that one component of the trade-off between egg size and clutch size is under much tighter genetic control than the other. Thus, the phenotypic trade-off between egg size and egg number in keelback snakes occurs because each female snake must allocate a finite amount of energy into eggs of a genetically determined size.

Female strobili incidence in a Minnesota population of black spruce: heritability and correlation with height growth

Treesearch

C. Dana Nelson; C. A. Mohn

1989-01-01

Significant family variation in female strobili incidence, ripeness-to-flower and production were found in a Minnesota black spruce (Picea mariana (Mill.) B.S.P.) population tested at four locations. Heritability estimates indicated that gain in early flowering from selection would be possible. Height growth through age 12 years was positively correlated (genetic and...

Heritability of Intraindividual Mean and Variability of Positive and Negative Affect.

PubMed

Zheng, Yao; Plomin, Robert; von Stumm, Sophie

2016-12-01

Positive affect (e.g., attentiveness) and negative affect (e.g., upset) fluctuate over time. We examined genetic influences on interindividual differences in the day-to-day variability of affect (i.e., ups and downs) and in average affect over the duration of a month. Once a day, 17-year-old twins in the United Kingdom ( N = 447) rated their positive and negative affect online. The mean and standard deviation of each individual's daily ratings across the month were used as the measures of that individual's average affect and variability of affect. Analyses revealed that the average of negative affect was significantly heritable (.53), but the average of positive affect was not; instead, the latter showed significant shared environmental influences (.42). Fluctuations across the month were significantly heritable for both negative affect (.54) and positive affect (.34). The findings support the two-factor theory of affect, which posits that positive affect is more situational and negative affect is more dispositional.

Heritability of Intraindividual Mean and Variability of Positive and Negative Affect

PubMed Central

Zheng, Yao; Plomin, Robert; von Stumm, Sophie

2016-01-01

Positive affect (e.g., attentiveness) and negative affect (e.g., upset) fluctuate over time. We examined genetic influences on interindividual differences in the day-to-day variability of affect (i.e., ups and downs) and in average affect over the duration of a month. Once a day, 17-year-old twins in the United Kingdom (N = 447) rated their positive and negative affect online. The mean and standard deviation of each individual’s daily ratings across the month were used as the measures of that individual’s average affect and variability of affect. Analyses revealed that the average of negative affect was significantly heritable (.53), but the average of positive affect was not; instead, the latter showed significant shared environmental influences (.42). Fluctuations across the month were significantly heritable for both negative affect (.54) and positive affect (.34). The findings support the two-factor theory of affect, which posits that positive affect is more situational and negative affect is more dispositional. PMID:27729566

Transmissibility and familiality of NEO personality dimensions in a sample of Korean families with schizophrenia.

PubMed

Kim, Soo Yeon; Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In

2018-02-01

Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of Neuroticism-Extraversion-Openness to experience (NEO) personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD).We have recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We have used NEO questionnaires for measuring personality and symptomatic dimensions. Heritabilities of personality dimensions in total 543 family members were estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Personality dimensions in total family members were compared with those in 307 healthy unrelated controls for measuring the familialities using ANOVA analysis.Four of the 5 NEO variables were significantly heritable and were included in the subsequent analyses. The 3 groups (control, unaffected first-degree relative, case) were found to be significantly different and with the expected order of average group scores for all heritable dimensions.Our results show that the aberrations in several personality dimensions could form the complexity of schizophrenic syndrome as a result of genetic-environment coactions or interactions in spite of some limitations (recruited family, phenotyping).

IgA measurements in over 12 000 Swedish twins reveal sex differential heritability and regulatory locus near CD30L

PubMed Central

Viktorin, Alexander; Frankowiack, Marcel; Padyukov, Leonid; Chang, Zheng; Melén, Erik; Sääf, Annika; Kull, Inger; Klareskog, Lars; Hammarström, Lennart; Magnusson, Patrik K.E.

2014-01-01

In a broad attempt to improve the understanding of the genetic regulation of serum IgA levels, the heritability was estimated in over 12 000 Swedish twins, and a genome-wide association study was conducted in a subsample of 9617. Using the classical twin model the heritability was found to be significantly larger among females (61%) compared with males (21%), while contribution from shared environment (20%) was only seen for males. By modeling the genetic relationship matrix with IgA levels, we estimate that a substantial proportion (31%) of variance in IgA levels can ultimately be explained by the investigated SNPs. The genome-wide association study revealed significant association to two loci: (i) rs6928791 located on chromosome 6, 22 kb upstream of the gene SAM and SH3 domain containing 1 (SASH1) and (ii) rs13300483 on chromosome 9, situated 12 kb downstream the CD30 ligand (CD30L) encoding gene. The association to rs13300483 was replicated in two additional independent Swedish materials. The heritability of IgA levels is moderate and can partly be attributable to common variation in the CD30L locus. PMID:24676358

Genetic parameter estimation for long endurance trials in the Uruguayan Criollo horse.

PubMed

López-Correa, R D; Peñagaricano, F; Rovere, G; Urioste, J I

2018-06-01

The aim of this study was to estimate the genetic parameters of performance in a 750-km, 15-day ride in Criollo horses. Heritability (h 2 ) and maternal lineage effects (mt 2 ) were obtained for rank, a relative placing measure of performance. Additive genetic and maternal lineage (rmt) correlations among five medium-to-high intensity phase ranks (pRK) and final rank (RK) were also estimated. Individual records from 1,236 Criollo horses from 1979 to 2012 were used. A multivariate threshold animal model was applied to the pRK and RK. Heritability was moderate to low (0.156-0.275). Estimates of mt 2 were consistently low (0.04-0.06). Additive genetic correlations between individual pRK and RK were high (0.801-0.924), and the genetic correlations between individual pRKs ranged from 0.763 to 0.847. The pRK heritabilities revealed that some phases were explained by a greater additive component, whereas others showed stronger genetic relationships with RK. Thus, not all pRK may be considered as similar measures of performance in competition. © 2018 Blackwell Verlag GmbH.

The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

PubMed

Krapohl, Eva; Rimfeld, Kaili; Shakeshaft, Nicholas G; Trzaskowski, Maciej; McMillan, Andrew; Pingault, Jean-Baptiste; Asbury, Kathryn; Harlaar, Nicole; Kovas, Yulia; Dale, Philip S; Plomin, Robert

2014-10-21

Because educational achievement at the end of compulsory schooling represents a major tipping point in life, understanding its causes and correlates is important for individual children, their families, and society. Here we identify the general ingredients of educational achievement using a multivariate design that goes beyond intelligence to consider a wide range of predictors, such as self-efficacy, personality, and behavior problems, to assess their independent and joint contributions to educational achievement. We use a genetically sensitive design to address the question of why educational achievement is so highly heritable. We focus on the results of a United Kingdom-wide examination, the General Certificate of Secondary Education (GCSE), which is administered at the end of compulsory education at age 16. GCSE scores were obtained for 13,306 twins at age 16, whom we also assessed contemporaneously on 83 scales that were condensed to nine broad psychological domains, including intelligence, self-efficacy, personality, well-being, and behavior problems. The mean of GCSE core subjects (English, mathematics, science) is more heritable (62%) than the nine predictor domains (35-58%). Each of the domains correlates significantly with GCSE results, and these correlations are largely mediated genetically. The main finding is that, although intelligence accounts for more of the heritability of GCSE than any other single domain, the other domains collectively account for about as much GCSE heritability as intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE. We conclude that the high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence

PubMed Central

Krapohl, Eva; Rimfeld, Kaili; Shakeshaft, Nicholas G.; Trzaskowski, Maciej; McMillan, Andrew; Pingault, Jean-Baptiste; Asbury, Kathryn; Harlaar, Nicole; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

2014-01-01

Because educational achievement at the end of compulsory schooling represents a major tipping point in life, understanding its causes and correlates is important for individual children, their families, and society. Here we identify the general ingredients of educational achievement using a multivariate design that goes beyond intelligence to consider a wide range of predictors, such as self-efficacy, personality, and behavior problems, to assess their independent and joint contributions to educational achievement. We use a genetically sensitive design to address the question of why educational achievement is so highly heritable. We focus on the results of a United Kingdom-wide examination, the General Certificate of Secondary Education (GCSE), which is administered at the end of compulsory education at age 16. GCSE scores were obtained for 13,306 twins at age 16, whom we also assessed contemporaneously on 83 scales that were condensed to nine broad psychological domains, including intelligence, self-efficacy, personality, well-being, and behavior problems. The mean of GCSE core subjects (English, mathematics, science) is more heritable (62%) than the nine predictor domains (35–58%). Each of the domains correlates significantly with GCSE results, and these correlations are largely mediated genetically. The main finding is that, although intelligence accounts for more of the heritability of GCSE than any other single domain, the other domains collectively account for about as much GCSE heritability as intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE. We conclude that the high heritability of educational achievement reflects many genetically influenced traits, not just intelligence. PMID:25288728

Heritability analyses of IQ scores: science or numerology?

PubMed

Layzer, D

1974-03-29

Estimates of IQ heritability are subject to a variety of systematic errors. The IQ scores themselves contain uncontrollable, systematic errors of unknown magnitude. These arise because IQ scores, unlike conventional physical and biological measurements, have a purely instrumental definition. The effects of these errors are apparent in the very large discrepancies among IQ correlations measured by different investigators. Genotype-environment correlations, whose effects can sometimes be minimized, if not wholly eliminated, in experiments with plants and animals, are nearly always important in human populations. The absence of significant effects arising from genotype-environment correlations is a necessary condition for the applicability of conventional heritability analysis to phenotypically plastic traits. When this condition fails, no quantitative inferences about heritability can be drawn from measured phenotypic variances and covariances, except under special conditions that are unlikely to be satisfied by phenotypically plastic traits in human populations. Inadequate understanding of the precise environmental factors relevant to the development of specific behavioral traits is an important source of systematic errors, as is the inability to allow adequately for the effects of assortative mating and gene-gene interaction. Systematic cultural differences and differences in psychological environment among races and among sociocco-nomic groups vitiate any attempt to draw from IQ data meaningful inferences about genetic differences. Estimates based on phenotypic correlations between separated monozygotic twins-usually considered to be the most reliable kind of estimates-are vitiated by systematic errors inherent in IQ tests, by the presence of genotype-environment correlation, and by the lack of detailed understanding of environmental factors relevant to the development of behavioral traits. Other kinds of estimates are beset, in addition, by systematic errors arising from incomplete allowance for the effects of assortative mating and from gene-gene interactions. The only potentially useful data are phenotypic correlations between unrelated foster children reared together, which could, in principle, yield lower limits for e(2). Available data indicate that, for unrelated foster children reared together, the broad heritability (h(2)) may lie between 0.0 and 0.5. This estimate does not apply to populations composed of children reared by their biological parents or by near relatives. For such populations the heritability of IQ remains undefined. The only data that might yield meaningful estimates ot narrow heritability are phenotypic correlations between half-sibs reared in statistically independent environments. No useful data of this kind are available. Intervention studies like Heber's Milwaukee Project afford an alternative and comparatively direct way of studying the plasticity of cognitive and other behavioral traits in human populations. Results obtained so far strongly suggest that the development of cognitive skills is highly sensitive to variations in environmental factors. These conclusions have three obvious implications for the broader issues mentioned at the beginning of this article. 1) Published analyses of IQ data provide no support whatever for Jensen's thesis that inequalities in cognitive performance are due largely to genetic differences. As Lewontin (8) has clearly shown, the value of the broad heritability of IQ is in any case only marginally relevant to this question. I have argued that conventional estimates of the broad heritability of IQ are invalid and that the only data on which potentially valid estimates might be based are consistent with a broad heritability of less than 0.5. On the other hand, intervention studies, if their findings prove to be replicable, would directly establish that, under suitable conditions, the offspring of parents whose cognitive skills are so poorly developed as to exclude them from all but the most menial occupations can achieve what are regarded as distinctly high levels of cognitive performance. Thus, despite the fact that children differ suibstantially in cognitive aptitudes and appetites, and despite the very high probability that these differences have a substantial genetic component, available scientific evidence strongly suggests that environmental factors are responsible for the failure of children not suffering from specific neurological disorders to achieve adequate levels of cognitive performance. 2) Under prevailing social conditions, no valid inferences can be drawn from IQ data concerning systematic genetic differences among races or socioeconomic groups. Research along present lines directed toward this end-whatever its ethical status-is scientifically worthless. 3) Since there are no suitable data for estimating the narrow heritability of IQ, it seems pointless to speculate about the prospects for a hereditary meritocracy based on IQ.

Genome-wide Association Analysis of Kernel Weight in Hard Winter Wheat

USDA-ARS?s Scientific Manuscript database

Wheat kernel weight is an important and heritable component of wheat grain yield and a key predictor of flour extraction. Genome-wide association analysis was conducted to identify genomic regions associated with kernel weight and kernel weight environmental response in 8 trials of 299 hard winter ...

Etiology of Triarchic Psychopathy Dimensions in Chimpanzees (Pan troglodytes)

PubMed Central

Latzman, Robert D.; Patrick, Christopher J.; Freeman, Hani J.; Schapiro, Steven J.; Hopkins, William D.

2016-01-01

The current study undertook analyses of genealogical data from a sample of 178 socially-housed chimpanzees (Pan troglodytes) with well-documented pedigrees, to clarify the etiologic bases of triarchic psychopathy dimensions and the influence of early social rearing experiences. Whereas biometric analyses for the full sample indicated significant heritability for the boldness dimension of psychopathy only, heritability estimates varied by early rearing, with all three triarchic dimensions showing significant heritabilities among mother-reared but not nursery-reared apes. For mother-reared apes, both genes and environment contributed to covariance between meanness and disinhibition, whereas environment contributed mainly to covariation between these dimensions and boldness. Results indicate contributions of both genes and environment to psychopathic tendencies, with an important role for early-rearing in their relative contributions to distinct phenotypic subdimensions. In conjunction with findings from human studies, results provide valuable insights into core biobehavioral processes relevant to psychological illness and health. PMID:28503367

Heritability and quantitative genetic divergence of serotiny, a fire-persistence plant trait

PubMed Central

Hernández-Serrano, Ana; Verdú, Miguel; Santos-del-Blanco, Luís; Climent, José; González-Martínez, Santiago C.; Pausas, Juli G.

2014-01-01

Background and Aims Although it is well known that fire acts as a selective pressure shaping plant phenotypes, there are no quantitative estimates of the heritability of any trait related to plant persistence under recurrent fires, such as serotiny. In this study, the heritability of serotiny in Pinus halepensis is calculated, and an evaluation is made as to whether fire has left a selection signature on the level of serotiny among populations by comparing the genetic divergence of serotiny with the expected divergence of neutral molecular markers (QST–FST comparison). Methods A common garden of P. halepensis was used, located in inland Spain and composed of 145 open-pollinated families from 29 provenances covering the entire natural range of P. halepensis in the Iberian Peninsula and Balearic Islands. Narrow-sense heritability (h2) and quantitative genetic differentiation among populations for serotiny (QST) were estimated by means of an ‘animal model’ fitted by Bayesian inference. In order to determine whether genetic differentiation for serotiny is the result of differential natural selection, QST estimates for serotiny were compared with FST estimates obtained from allozyme data. Finally, a test was made of whether levels of serotiny in the different provenances were related to different fire regimes, using summer rainfall as a proxy for fire regime in each provenance. Key Results Serotiny showed a significant narrow-sense heritability (h2) of 0·20 (credible interval 0·09–0·40). Quantitative genetic differentiation among provenances for serotiny (QST = 0·44) was significantly higher than expected under a neutral process (FST = 0·12), suggesting adaptive differentiation. A significant negative relationship was found between the serotiny level of trees in the common garden and summer rainfall of their provenance sites. Conclusions Serotiny is a heritable trait in P. halepensis, and selection acts on it, giving rise to contrasting serotiny levels among populations depending on the fire regime, and supporting the role of fire in generating genetic divergence for adaptive traits. PMID:25008363

Effect of dietary fat intake and genetics on fat taste sensitivity: a co-twin randomized controlled trial.

PubMed

Costanzo, Andrew; Nowson, Caryl; Orellana, Liliana; Bolhuis, Dieuwerke; Duesing, Konsta; Keast, Russell

2018-05-01

Individuals with impaired fat taste (FT) sensitivity have reduced satiety responses after consuming fatty foods, leading to increased dietary fat intake. Habitual consumption of dietary fat may modulate sensitivity to FT, with high consumption decreasing sensitivity [increasing fatty acid taste threshold (FATT)] and low consumption increasing sensitivity (decreasing FATT). However, some individuals may be less susceptible to diet-mediated changes in FATT due to variations in gene expression. The objective of this study was to determine the effect of an 8-wk low-fat or high-fat diet on FATT while maintaining baseline weight (<2.0 kg variation) to assess heritability and to explore the effect of genetics on diet-mediated changes in FATT. A co-twin randomized controlled trial including 44 pairs (mean ± SD age: 43.7 ± 15.4 y; 34 monozygotic, 10 dizygotic; 33 women, 10 men, 1 gender-discordant) was conducted. Twins within a pair were randomly allocated to an 8-wk low-fat (<20% of energy from fat) or high-fat (>35% of energy from fat) diet. FATT was assessed by a 3-alternate forced choice methodology and transformed to an ordinal scale (FT rank) at baseline and at 4 and 8 wk. Linear mixed models were fit to assess diet effect on FT rank and diet effect modification due to zygosity. A variance components model was fit to calculate baseline heritability. There was a significant time × diet interaction for FT rank after the 8-wk trial (P < 0.001), with the same conclusions for the subset of participants maintaining baseline weight (low-fat; n = 32; high-fat: n = 35). There was no evidence of zygosity effect modification (interaction of time × diet × zygosity: P = 0.892). Heritability of baseline FT rank was 8%. There appears to be little to no genetic contribution on heritability of FATT or diet-mediated changes to FATT. Rather, environment, specifically dietary fat intake, is the main influencer of FT sensitivity, regardless of body weight. This trial was registered with the Australian New Zealand Clinical Trials Registry at http://www.anzctr.org.au/ as ACTRN12613000466741.

Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder.

PubMed

Hare, Elizabeth; Contreras, Javier; Raventos, Henriette; Flores, Deborah; Jerez, Alvaro; Nicolini, Humberto; Ontiveros, Alfonso; Almasy, Laura; Escamilla, Michael

2012-02-01

Bipolar disorder (BPD) has been associated with variations in personality dimensions, but the nature of this relationship has been unclear. In this study, the heritabilities of BPD and the Big Five personality factors and the genetic correlations between BPD and personality factors are reported. The participants in this study were 1073 individuals from 172 families of Mexican or Central American ancestry. Heritabilities and genetic correlations were calculated under a polygenic model using the maximum-likelihood method of obtaining variance components implemented in the SOLAR software package. Heritabilities of 0.49, 0.43, and 0.43 were found for the narrowest phenotype (schizoaffective bipolar and bipolar I), the intermediate phenotype (schizoaffective bipolar, bipolar I, and bipolar II), and the broadest phenotype (schizoaffective bipolar, bipolar I, bipolar II, and recurrent depression), respectively. For the Big Five personality factors, heritabilities were 0.25 for agreeableness, 0.24 for conscientiousness, 0.24 for extraversion, 0.23 for neuroticism, and 0.32 for openness to experience. For the narrowest phenotype, a significant negative correlation (-0.32) with extraversion was found. For the broadest phenotype, negative correlations were found for agreeableness (-0.35), conscientiousness (-0.39), and extraversion (-0.44). A positive correlation (0.37) was found with neuroticism. It is not possible to determine whether aspects of personality are factors in the development of bipolar disorder or vice versa. The short form of the NEO does not provide the ability to examine in detail which facets of extraversion are most closely related to bipolar disorder or to compare our results with studies that have used the long version of the scale. This study establishes a partial genetic basis for the Big Five personality factors in this set of families, while the environmental variances demonstrate that non-genetic factors are also important in their influence on bipolar and personality phenotypes. BPD may be most associated with decreased extraversion (less interaction with one's surroundings) because patients spend more time in depressive than manic states. Copyright © 2011. Published by Elsevier B.V.

Heritability of Craniofacial Structures in Normal Subjects and Patients with Sleep Apnea

PubMed Central

Chi, Luqi; Comyn, Francois-Louis; Keenan, Brendan T.; Cater, Jacqueline; Maislin, Greg; Pack, Allan I.; Schwab, Richard J.

2014-01-01

Objectives: Accumulating evidence has shown that there is a genetic contribution to obstructive sleep apnea (OSA).The objectives were to use magnetic resonance imaging (MRI) cephalometry to (1) confirm heritability of craniofacial risk factors for OSA previously shown by cephalometrics; and (2) examine the heritability of new craniofacial structures that are measurable with MRI. Design: A sib pair “quad” design examining apneics, apneic siblings, controls, and control siblings. The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for differences in age, sex, ethnicity, height, and weight. Setting: Academic medical center. Patients: We examined 55 apneic probands (apnea-hypopnea index [AHI]: 46.8 ± 33.5 events/h), 55 proband siblings (AHI: 11.1 ± 15.9 events/h), 55 controls (AHI: 2.2 ± 1.7 events/h), and 55 control siblings (AHI: 4.1 ± 4.0 events/h). Interventions: N/A. Measurements and Results: Five independent domains reflecting different aspects of the craniofacial structure were examined. We confirmed heritability of sella–nasion–subspinale (38%, P = 0.002), saddle angle (55%, P < 0.0001), mandibular length (24%, P = 0.02) and lower facial height (33%, P = 0.006) previously measured by cephalometry. In addition, the current study added new insights by demonstrating significant heritability of mandibular width (30%, P = 0.005), maxillary width (47%, P < 0.0001), distance from the hyoid bone to the retropogonion (36%, P = 0.0018) and size of the oropharyngeal space (31%, P = 0.004). Finally, our data indicate that heritability of the craniofacial structures is similar in normal patients and those with apnea. Conclusions: The data support our a priori hypothesis that the craniofacial structures that have been associated with obstructive sleep apnea (OSA) are heritable. We have demonstrated heritability for several intermediate craniofacial phenotypes for OSA. Thus, we believe that future studies should be able to identify genes associated with these intermediate craniofacial phenotypes. Citation: Chi L, Comyn FL, Keenan BT, Cater J, Maislin G, Pack AI, Schwab RJ. Heritability of craniofacial structures in normal subjects and patients with sleep apnea. SLEEP 2014;37(10):1689-1698. PMID:25197806

Selection and breeding of honey bees for higher or lower collection of avocado nectar.

PubMed

Afik, Ohad; Dag, Arnon; Yeselson, Yelena; Schaffer, Arthur; Shafir, Sharoni

2010-04-01

Intensive activity of honey bees, Apis mellifera L., is essential for high fruit set in avocado, Persea americana Mill., orchards, but even when hives are located inside the orchard, many bees still search for alternative blooms. We tested for a possible genetic component for a preference of avocado bloom relative to competing bloom. The honey from each hive was extracted at the end of the avocado bloom and the concentration of perseitol, a carbohydrate that is unique to avocado, was analyzed as a measure for avocado foraging. During the first year, five bee strains were compared in three different sites in Israel. Significant differences were found between strains in honey perseitol concentrations, suggesting differences in their efficiency as avocado pollinators, although these differences were site dependent. At two sites, colonies with the highest and lowest perseitol concentrations were selected as parental "high" and "low" lines. Queens were raised from the selected colonies and were instrumentally inseminated by drones from other colonies of this line. During the second and third years, colonies with inseminated queens were introduced to the avocado orchards, together with the selected colonies still surviving from the previous year. Colonies of the high line had greater perseitol concentrations than those of the low line. Selected colonies that survived from the previous year performed consistently vis-à-vis perseitol concentration, in the second year of testing. Heritability value of 0.22 was estimated based on regression of offspring on midparent. The results reveal a heritable component for willingness of honey bees to collect avocado nectar.

A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets

PubMed Central

Sanjak, Jaleal S.; Long, Anthony D.; Thornton, Kevin R.

2017-01-01

The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation. PMID:28103232

The Human Microbiome and the Missing Heritability Problem

PubMed Central

Sandoval-Motta, Santiago; Aldana, Maximino; Martínez-Romero, Esperanza; Frank, Alejandro

2017-01-01

The “missing heritability” problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this “missing heritability” have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies. PMID:28659968

Neural Mechanism Underling Comprehension of Narrative Speech and Its Heritability: Study in a Large Population.

PubMed

Babajani-Feremi, Abbas

2017-09-01

Comprehension of narratives constitutes a fundamental part of our everyday life experience. Although the neural mechanism of auditory narrative comprehension has been investigated in some studies, the neural correlates underlying this mechanism and its heritability remain poorly understood. We investigated comprehension of naturalistic speech in a large, healthy adult population (n = 429; 176/253 M/F; 22-36 years of age) consisting of 192 twin pairs (49 monozygotic and 47 dizygotic pairs) and 237 of their siblings. We used high quality functional MRI datasets from the Human Connectome Project (HCP) in which a story-based paradigm was utilized for the auditory narrative comprehension. Our results revealed that narrative comprehension was associated with activations of the classical language regions including superior temporal gyrus (STG), middle temporal gyrus (MTG), and inferior frontal gyrus (IFG) in both hemispheres, though STG and MTG were activated symmetrically and activation in IFG were left-lateralized. Our results further showed that the narrative comprehension was associated with activations in areas beyond the classical language regions, e.g. medial superior frontal gyrus (SFGmed), middle frontal gyrus (MFG), and supplementary motor area (SMA). Of subcortical structures, only the hippocampus was involved. The results of heritability analysis revealed that the oral reading recognition and picture vocabulary comprehension were significantly heritable (h 2  > 0.56, p < 10 - 13 ). In addition, the extent of activation of five areas in the left hemisphere, i.e. STG, IFG pars opercularis, SFGmed, SMA, and precuneus, and one area in the right hemisphere, i.e. MFG, were significantly heritable (h 2  > 0.33, p < 0.0004). The current study, to the best of our knowledge, is the first to investigate auditory narrative comprehension and its heritability in a large healthy population. Referring to the excellent quality of the HCP data, our results can clarify the functional contributions of linguistic and extra-linguistic cortices during narrative comprehension.

A test of the facultative calibration/reactive heritability model of extraversion

PubMed Central

Haysom, Hannah J.; Mitchem, Dorian G.; Lee, Anthony J.; Wright, Margaret J.; Martin, Nicholas G.; Keller, Matthew C.; Zietsch, Brendan P.

2015-01-01

A model proposed by Lukaszewski and Roney (2011) suggests that each individual’s level of extraversion is calibrated to other traits that predict the success of an extraverted behavioural strategy. Under ‘facultative calibration’, extraversion is not directly heritable, but rather exhibits heritability through its calibration to directly heritable traits (“reactive heritability”). The current study uses biometrical modelling of 1659 identical and non-identical twins and their siblings to assess whether the genetic variation in extraversion is calibrated to variation in facial attractiveness, intelligence, height in men and body mass index (BMI) in women. Extraversion was significantly positively correlated with facial attractiveness in both males (r=.11) and females (r=.18), but correlations between extraversion and the other variables were not consistent with predictions. Further, twin modelling revealed that the genetic variation in facial attractiveness did not account for a substantial proportion of the variation in extraversion in either males (2.4%) or females (0.5%). PMID:26880866

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.

PubMed

Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L; Kreiner, Eskil; Chesi, Alessandra; Zemel, Babette S; Bønnelykke, Klaus; Boer, Cindy G; Ahluwalia, Tarunveer S; Bisgaard, Hans; Evangelou, Evangelos; Heppe, Denise H M; Bonewald, Lynda F; Gorski, Jeffrey P; Ghanbari, Mohsen; Demissie, Serkalem; Duque, Gustavo; Maurano, Matthew T; Kiel, Douglas P; Hsu, Yi-Hsiang; C J van der Eerden, Bram; Ackert-Bicknell, Cheryl; Reppe, Sjur; Gautvik, Kaare M; Raastad, Truls; Karasik, David; van de Peppel, Jeroen; Jaddoe, Vincent W V; Uitterlinden, André G; Tobias, Jonathan H; Grant, Struan F A; Bagos, Pantelis G; Evans, David M; Rivadeneira, Fernando

2017-07-25

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs.

PubMed

Wilson, Bethany J; Nicholas, Frank W; James, John W; Wade, Claire M; Tammen, Imke; Raadsma, Herman W; Castle, Kao; Thomson, Peter C

2012-01-01

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.

Estimating the potential for adaptation of corals to climate warming.

PubMed

Császár, Nikolaus B M; Ralph, Peter J; Frankham, Richard; Berkelmans, Ray; van Oppen, Madeleine J H

2010-03-18

The persistence of tropical coral reefs is threatened by rapidly increasing climate warming, causing a functional breakdown of the obligate symbiosis between corals and their algal photosymbionts (Symbiodinium) through a process known as coral bleaching. Yet the potential of the coral-algal symbiosis to genetically adapt in an evolutionary sense to warming oceans is unknown. Using a quantitative genetics approach, we estimated the proportion of the variance in thermal tolerance traits that has a genetic basis (i.e. heritability) as a proxy for their adaptive potential in the widespread Indo-Pacific reef-building coral Acropora millepora. We chose two physiologically different populations that associate respectively with one thermo-tolerant (Symbiodinium clade D) and one less tolerant symbiont type (Symbiodinium C2). In both symbiont types, pulse amplitude modulated (PAM) fluorometry and high performance liquid chromatography (HPLC) analysis revealed significant heritabilities for traits related to both photosynthesis and photoprotective pigment profile. However, quantitative real-time polymerase chain reaction (qRT-PCR) assays showed a lack of heritability in both coral host populations for their own expression of fundamental stress genes. Coral colony growth, contributed to by both symbiotic partners, displayed heritability. High heritabilities for functional key traits of algal symbionts, along with their short clonal generation time and high population sizes allow for their rapid thermal adaptation. However, the low overall heritability of coral host traits, along with the corals' long generation time, raise concern about the timely adaptation of the coral-algal symbiosis in the face of continued rapid climate warming.

Estimating the Potential for Adaptation of Corals to Climate Warming

PubMed Central

Császár, Nikolaus B. M.; Ralph, Peter J.; Frankham, Richard; Berkelmans, Ray; van Oppen, Madeleine J. H.

2010-01-01

The persistence of tropical coral reefs is threatened by rapidly increasing climate warming, causing a functional breakdown of the obligate symbiosis between corals and their algal photosymbionts (Symbiodinium) through a process known as coral bleaching. Yet the potential of the coral-algal symbiosis to genetically adapt in an evolutionary sense to warming oceans is unknown. Using a quantitative genetics approach, we estimated the proportion of the variance in thermal tolerance traits that has a genetic basis (i.e. heritability) as a proxy for their adaptive potential in the widespread Indo-Pacific reef-building coral Acropora millepora. We chose two physiologically different populations that associate respectively with one thermo-tolerant (Symbiodinium clade D) and one less tolerant symbiont type (Symbiodinium C2). In both symbiont types, pulse amplitude modulated (PAM) fluorometry and high performance liquid chromatography (HPLC) analysis revealed significant heritabilities for traits related to both photosynthesis and photoprotective pigment profile. However, quantitative real-time polymerase chain reaction (qRT-PCR) assays showed a lack of heritability in both coral host populations for their own expression of fundamental stress genes. Coral colony growth, contributed to by both symbiotic partners, displayed heritability. High heritabilities for functional key traits of algal symbionts, along with their short clonal generation time and high population sizes allow for their rapid thermal adaptation. However, the low overall heritability of coral host traits, along with the corals' long generation time, raise concern about the timely adaptation of the coral-algal symbiosis in the face of continued rapid climate warming. PMID:20305781

Heritability Analyses of IQ Scores: Science or Numerology?

ERIC Educational Resources Information Center

Layzer, David

1974-01-01

Examines limitations of the heritability concept and heritability analysis, and discusses a conventional application of heritability analysis, IQ scores as measurements of a phenotypic character, the heritability of IQ, and the relationship of IQ and race. (JR)

Preliminary report of ecological factors influencing incidence and severity of beech bark disease in the Appalachian region

Treesearch

David P. McCann; William L. MacDonald

2013-01-01

Resistance to Cryptococcus fagisuga, a primary component of the beech bark disease (BBD) complex, is heritable. Reportedly about 1-2 percent of American beech (Fagus grandifolia Ehrh.) are genetically resistant to C. fagisuga. This project is designed to identify environmental factors contributing to BBD...

Identification of Traits Associated with Stuttering

ERIC Educational Resources Information Center

Subramanian, Anu; Yairi, Ehud

2006-01-01

Stuttering has been considered a heritable disorder since the 1930s. There have been different models of transmission that have been proposed most involving a polygenic component with or without a major locus. In spite of these models, the characteristics being transmitted are not known. This study used two different tasks--a tapping task that is…

The heritable basis of gene-environment interactions in cardiometabolic traits.

PubMed

Poveda, Alaitz; Chen, Yan; Brändström, Anders; Engberg, Elisabeth; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Kurbasic, Azra; Franks, Paul W

2017-03-01

Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions. Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h 2 ) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction. Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

Twin study on heritability of activity, attention, and impulsivity as assessed by objective measures.

PubMed

Heiser, Philip; Heinzel-Gutenbrunner, Monika; Frey, Joachim; Smidt, Judith; Grabarkiewicz, Justyna; Friedel, Susann; Kühnau, Wolfgang; Schmidtke, Jörg; Remschmidt, Helmut; Hebebrand, Johannes

2006-05-01

The purpose of this study was to assess heritability of activity, attention, and impulsivity by comparing young monozygotic (MZ) twins with dizygotic (DZ) twins using objective measures. The OPTAx test is an infrared motion analysis to record the movement pattern during a continuous performance test. Seventeen MZ and 12 same sexed DZ twin pairs in the range of 6 to 12 years were tested. The zygosity was determined by DNA-fingerprinting. The measures under investigation were activity (microevents and spatial scaling), impulsivity (errors of commission), and attention (accuracy and variability). For statistical analyses, the classical model of Falconer and the ACE and ADE genetic model for twin data were applied in order to estimate the proportion of the variance in activity, impulsivity and attention that is due to genetic effects. The respective coefficients of intraclass correlations in MZ twins ranged between .35 and .65 whereas for DZ twins the correlations were between .12 and .88. The heritability estimates resulting from both models were about 30% for 4 of the 5 measures, but none of these was significantly different from 0. We found no significant influence of genetic factors for activity, attention, and impulsivity. The authors conclude that further investigation of heritability of ADHD is necessary using larger sample sizes and objective measures.

IgA measurements in over 12 000 Swedish twins reveal sex differential heritability and regulatory locus near CD30L.

PubMed

Viktorin, Alexander; Frankowiack, Marcel; Padyukov, Leonid; Chang, Zheng; Melén, Erik; Sääf, Annika; Kull, Inger; Klareskog, Lars; Hammarström, Lennart; Magnusson, Patrik K E

2014-08-01

In a broad attempt to improve the understanding of the genetic regulation of serum IgA levels, the heritability was estimated in over 12 000 Swedish twins, and a genome-wide association study was conducted in a subsample of 9617. Using the classical twin model the heritability was found to be significantly larger among females (61%) compared with males (21%), while contribution from shared environment (20%) was only seen for males. By modeling the genetic relationship matrix with IgA levels, we estimate that a substantial proportion (31%) of variance in IgA levels can ultimately be explained by the investigated SNPs. The genome-wide association study revealed significant association to two loci: (i) rs6928791 located on chromosome 6, 22 kb upstream of the gene SAM and SH3 domain containing 1 (SASH1) and (ii) rs13300483 on chromosome 9, situated 12 kb downstream the CD30 ligand (CD30L) encoding gene. The association to rs13300483 was replicated in two additional independent Swedish materials. The heritability of IgA levels is moderate and can partly be attributable to common variation in the CD30L locus. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study.

PubMed

Dirani, Mohamed; Chamberlain, Matthew; Shekar, Sri N; Islam, Amirul F M; Garoufalis, Pam; Chen, Christine Y; Guymer, Robyn H; Baird, Paul N

2006-11-01

A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.

Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

PubMed

Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

2012-01-01

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8)) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4)) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

Genetic analysis of growth traits in Polled Nellore cattle raised on pasture in tropical region using Bayesian approaches.

PubMed

Lopes, Fernando Brito; Magnabosco, Cláudio Ulhôa; Paulini, Fernanda; da Silva, Marcelo Corrêa; Miyagi, Eliane Sayuri; Lôbo, Raysildo Barbosa

2013-01-01

Components of (co)variance and genetic parameters were estimated for adjusted weights at ages 120 (W120), 240 (W240), 365 (W365) and 450 (W450) days of Polled Nellore cattle raised on pasture and born between 1987 and 2010. Analyses were performed using an animal model, considering fixed effects: herd-year-season of birth and calf sex as contemporary groups and the age of cow as a covariate. Gibbs Samplers were used to estimate (co)variance components, genetic parameters and additive genetic effects, which accounted for great proportion of total variation in these traits. High direct heritability estimates for the growth traits were revealed and presented mean 0.43, 0.61, 0.72 and 0.67 for W120, W240, W365 and W450, respectively. Maternal heritabilities were 0.07 and 0.08 for W120 and W240, respectively. Direct additive genetic correlations between the weight at 120, 240, 365 and 450 days old were strong and positive. These estimates ranged from 0.68 to 0.98. Direct-maternal genetic correlations were negative for W120 and W240. The estimates ranged from -0.31 to -0.54. Estimates of maternal heritability ranged from 0.056 to 0.092 for W120 and from 0.064 to 0.096 for W240. This study showed that genetic progress is possible for the growth traits we studied, which is a novel and favorable indicator for an upcoming and promising Polled Zebu breed in Tropical regions. Maternal effects influenced the performance of weight at 120 and 240 days old. These effects should be taken into account in genetic analyses of growth traits by fitting them as a genetic or a permanent environmental effect, or even both. In general, due to a medium-high estimate of environmental (co)variance components, management and feeding conditions for Polled Nellore raised at pasture in tropical regions of Brazil needs improvement and growth performance can be enhanced.

Heritable variation in host tolerance and resistance inferred from a wild host-parasite system.

PubMed

Mazé-Guilmo, Elise; Loot, Géraldine; Páez, David J; Lefèvre, Thierry; Blanchet, Simon

2014-03-22

Hosts have evolved two distinct defence strategies against parasites: resistance (which prevents infection or limit parasite growth) and tolerance (which alleviates the fitness consequences of infection). However, heritable variation in resistance and tolerance and the genetic correlation between these two traits have rarely been characterized in wild host populations. Here, we estimate these parameters for both traits in Leuciscus burdigalensis, a freshwater fish parasitized by Tracheliastes polycolpus. We used a genetic database to construct a full-sib pedigree in a wild L. burdigalensis population. We then used univariate animal models to estimate inclusive heritability (i.e. all forms of genetic and non-genetic inheritance) in resistance and tolerance. Finally, we assessed the genetic correlation between these two traits using a bivariate animal model. We found significant heritability for resistance (H = 17.6%; 95% CI: 7.2-32.2%) and tolerance (H = 18.8%; 95% CI: 4.4-36.1%), whereas we found no evidence for the existence of a genetic correlation between these traits. Furthermore, we confirm that resistance and tolerance are strongly affected by environmental effects. Our results demonstrate that (i) heritable variation exists for parasite resistance and tolerance in wild host populations, and (ii) these traits can evolve independently in populations.

Facial averageness and genetic quality: Testing heritability, genetic correlation with attractiveness, and the paternal age effect.

PubMed

Lee, Anthony J; Mitchem, Dorian G; Wright, Margaret J; Martin, Nicholas G; Keller, Matthew C; Zietsch, Brendan P

2016-01-01

Popular theory suggests that facial averageness is preferred in a partner for genetic benefits to offspring. However, whether facial averageness is associated with genetic quality is yet to be established. Here, we computed an objective measure of facial averageness for a large sample ( N = 1,823) of identical and nonidentical twins and their siblings to test two predictions from the theory that facial averageness reflects genetic quality. First, we use biometrical modelling to estimate the heritability of facial averageness, which is necessary if it reflects genetic quality. We also test for a genetic association between facial averageness and facial attractiveness. Second, we assess whether paternal age at conception (a proxy of mutation load) is associated with facial averageness and facial attractiveness. Our findings are mixed with respect to our hypotheses. While we found that facial averageness does have a genetic component, and a significant phenotypic correlation exists between facial averageness and attractiveness, we did not find a genetic correlation between facial averageness and attractiveness (therefore, we cannot say that the genes that affect facial averageness also affect facial attractiveness) and paternal age at conception was not negatively associated with facial averageness. These findings support some of the previously untested assumptions of the 'genetic benefits' account of facial averageness, but cast doubt on others.

Heritable variation of sex pheromone composition and the potential for evolution of resistance to pheromone-based control of the Indian meal moth, Plodia interpunctella.

PubMed

Svensson, Glenn P; Ryne, Camilla; Löfstedt, Christer

2002-07-01

The short-term evolutionary effect of pheromone-based mating disruption on the mating ability of the Indian meal moth, Plodia interpunctella, was investigated. Three independent selection lines were established, and the mating ability of moths in plastic tents treated with high doses of pheromone and in control tents was compared for two consecutive generations. In addition, the heritability of the sex pheromone blend, measured as the ratio of two major pheromone components (Z,E)-9,12-tetradecadienyl acetate and (Z,E)-9,12-tetradecadienol, was estimated. Based on a mother-daughter regression analysis including 21 families, the heritability of the pheromone blend was 0.65 +/- 0.14, indicating a potential for evolutionary change of the character. However, no increase in mating ability of females in pheromone-treated tents or alteration of the pheromone blend was observed in any selection line when compared with control lines, indicating no or weak selection on the pheromone blend as well as other traits influencing mating ability of this species under the created mating disruption conditions. Factors contributing to the lack of selection effects are discussed.

Pollen-tube growth rates in Collinsia heterophylla (Plantaginaceae): one-donor crosses reveal heritability but no effect on sporophytic-offspring fitness.

PubMed

Lankinen, Asa; Maad, Johanne; Armbruster, W Scott

2009-04-01

Evolutionary change in response to natural selection will occur only if a trait confers a selective advantage and there is heritable variation. Positive connections between pollen traits and fitness have been found, but few studies of heritability have been conducted, and they have yielded conflicting results. To understand better the evolutionary significance of pollen competition and its potential role in sexual selection, the heritability of pollen tube-growth rate and the relationship between this trait and sporophytic offspring fitness were investigated in Collinsia heterophylla. Because the question being asked was if female function benefited from obtaining genetically superior fathers by enhancing pollen competition, one-donor (per flower) crosses were used in order to exclude confounding effects of post-fertilization competition/allocation caused by multiple paternity. Each recipient plant was crossed with an average of five pollen donors. Pollen-tube growth rate and sporophytic traits were measured in both generations. Pollen-tube growth rate in vitro differed among donors, and the differences were correlated with in vivo growth rate averaged over two to four maternal plants. Pollen-tube growth rate showed significant narrow-sense heritability and evolvability in a father-offspring regression. However, this pollen trait did not correlate significantly with sporophytic-offspring fitness. These results suggest that pollen-tube growth rate can respond to selection via male function. The data presented here do not provide any support for the hypothesis that intense pollen competition enhances maternal plant fitness through increased paternity by higher-quality sporophytic fathers, although this advantage cannot be ruled out. These data are, however, consistent with the hypothesis that pollen competition is itself selectively advantageous, through both male and female function, by reducing the genetic load among successful gametophytic fathers (pollen), and reducing inbreeding depression associated with self-pollination in plants with mix-mating systems.

Pollen-tube growth rates in Collinsia heterophylla (Plantaginaceae): one-donor crosses reveal heritability but no effect on sporophytic-offspring fitness

PubMed Central

Lankinen, Åsa; Maad, Johanne; Armbruster, W. Scott

2009-01-01

Background and Aims Evolutionary change in response to natural selection will occur only if a trait confers a selective advantage and there is heritable variation. Positive connections between pollen traits and fitness have been found, but few studies of heritability have been conducted, and they have yielded conflicting results. To understand better the evolutionary significance of pollen competition and its potential role in sexual selection, the heritability of pollen tube-growth rate and the relationship between this trait and sporophytic offspring fitness were investigated in Collinsia heterophylla. Methods Because the question being asked was if female function benefited from obtaining genetically superior fathers by enhancing pollen competition, one-donor (per flower) crosses were used in order to exclude confounding effects of post-fertilization competition/allocation caused by multiple paternity. Each recipient plant was crossed with an average of five pollen donors. Pollen-tube growth rate and sporophytic traits were measured in both generations. Key Results Pollen-tube growth rate in vitro differed among donors, and the differences were correlated with in vivo growth rate averaged over two to four maternal plants. Pollen-tube growth rate showed significant narrow-sense heritability and evolvability in a father–offspring regression. However, this pollen trait did not correlate significantly with sporophytic-offspring fitness. Conclusions These results suggest that pollen-tube growth rate can respond to selection via male function. The data presented here do not provide any support for the hypothesis that intense pollen competition enhances maternal plant fitness through increased paternity by higher-quality sporophytic fathers, although this advantage cannot be ruled out. These data are, however, consistent with the hypothesis that pollen competition is itself selectively advantageous, through both male and female function, by reducing the genetic load among successful gametophytic fathers (pollen), and reducing inbreeding depression associated with self–pollination in plants with mix-mating systems. PMID:19202136

Unique Genetic Loci Identified for Emotional Behavior in Control and Chronic Stress Conditions

DTIC Science & Technology

2014-10-21

Barcelona , Spain *Correspondence: Ryan Jankord, Applied Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Bldg. 840, 2510 Fifth St...heritability of behavioral traits measured in FC and EPM testing Broad-sense (H2) and narrow-sense (h2) heritability of expres- sion levels in the recombinant...Effect containing significant and/or suggestive peaks. Abbreviations in legend: Fear Conditioning ( FC ), elevated plus maze, (EPM), freezing to training

[Genetic aspects of the Stroop test].

PubMed

Nánási, Tibor; Katonai, Enikő Rózsa; Sasvári-Székely, Mária; Székely, Anna

2012-12-01

Impairment of executive control functions in depression is well documented, and performance on the Stroop Test is one of the most widely used markers to measure the decline. This tool provides reliable quantitative phenotype data that can be used efficiently in candidate gene studies investigating inherited components of executive control. Aim of the present review is to summarize research on genetic factors of Stroop performance. Interestingly, only a few such candidate gene studies have been carried out to date. Twin studies show a 30-60% heritability estimate for the Stroop test, suggesting a significant genetic component. A single genome-wide association study has been carried out on Stroop performance, and it did not show any significant association with any of the tested polymorphisms after correction for multiple testing. Candidate gene studies to date pointed to the polymorphisms of several neurotransmitter systems (dopamine, serotonin, acetylcholine) and to the role of the APOE ε4 allele. Surprisingly, little is known about the genetic role of neurothrophic factors and survival factors. In conclusion, further studies are needed for clarifying the genetic background of Stroop performance, characterizing attentional functions.

Linear measurements of the neurocranium are better indicators of population differences than those of the facial skeleton: comparative study of 1,961 skulls.

PubMed

Holló, Gábor; Szathmáry, László; Marcsik, Antónia; Barta, Zoltán

2010-02-01

The aim of this study is to individualize potential differences between two cranial regions used to differentiate human populations. We compared the neurocranium and the facial skeleton using skulls from the Great Hungarian Plain. The skulls date to the 1st-11th centuries, a long space of time that encompasses seven archaeological periods. We analyzed six neurocranial and seven facial measurements. The reduction of the number of variables was carried out using principal components analysis. Linear mixed-effects models were fitted to the principal components of each archaeological period, and then the models were compared using multiple pairwise tests. The neurocranium showed significant differences in seven cases between nonsubsequent periods and in one case, between two subsequent populations. For the facial skeleton, no significant results were found. Our results, which are also compared to previous craniofacial heritability estimates, suggest that the neurocranium is a more conservative region and that population differences can be pointed out better in the neurocranium than in the facial skeleton.

Violent men have more sons: further evidence for the generalized Trivers-Willard hypothesis (gTWH).

PubMed

Kanazawa, Satoshi

2006-04-21

The generalized Trivers-Willard hypothesis (gTWH) [Kanazawa, S., 2005a. Big and tall parents have more sons; further generalizations of the Trivers-Willard hypothesis. J. Theor. Biol. 235, 583-590] proposes that parents who possess any heritable trait which increases the male reproductive success at a greater rate than female reproductive success in a given environment have a higher-than-expected offspring sex ratio, and parents who possess any heritable trait which increases the female reproductive success at a greater rate than male reproductive success in a given environment have a lower-than-expected offspring sex ratio. One heritable trait which increases the reproductive success of sons significantly more than that of daughters in the ancestral environment is the tendency toward violence and aggression. I therefore predict that violent parents have a higher-than-expected offspring sex ratio (more sons). The analysis of both American samples and a British sample demonstrates that battered women, who are mated to violent men, have significantly more sons than daughters.

Familial Risks of Tourette Syndrome and Chronic Tic Disorders. A Population-Based Cohort Study.

PubMed

Mataix-Cols, David; Isomura, Kayoko; Pérez-Vigil, Ana; Chang, Zheng; Rück, Christian; Larsson, K Johan; Leckman, James F; Serlachius, Eva; Larsson, Henrik; Lichtenstein, Paul

2015-08-01

Tic disorders, including Tourette syndrome (TS) and chronic tic disorders (CTDs), are assumed to be strongly familial and heritable. Although gene-searching efforts are well under way, precise estimates of familial risk and heritability are lacking. Previous controlled family studies were small and typically conducted within specialist clinics, resulting in potential ascertainment biases. They were also underpowered to disentangle genetic from environmental factors that contribute to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (nonclinical) twin samples. To provide unbiased estimates of familial risk and heritability of tic disorders at the population level. In this population cohort, multigenerational family study, we used a validated algorithm to identify 4826 individuals diagnosed as having TS or CTDs (76.2% male) in the Swedish National Patient Register from January 1, 1969, through December 31, 2009. We studied risks for TS or CTDs in all biological relatives of probands compared with relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of tic disorders. The risk for tic disorders among relatives of probands with tic disorders increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (odds ratio [OR], 18.69; 95% CI, 14.53-24.05) were significantly higher than for second-degree relatives (OR, 4.58; 95% CI, 3.22-6.52) and third-degree relatives (OR, 3.07; 95% CI, 2.08-4.51). First-degree relatives at similar genetic distances (eg, parents, siblings, and offspring) had similar risks for tic disorders despite different degrees of shared environment. The risks for full siblings (50% genetic similarity; OR, 17.68; 95% CI, 12.90-24.23) were significantly higher than those for maternal half siblings (25% genetic similarity; OR, 4.41; 95% CI, 2.24-8.67) despite similar environmental exposures. The heritability of tic disorders was estimated to be 0.77 (95% CI, 0.70-0.85). There were no differences in familial risk or heritability between male and female patients. Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions.

Heritable Variation for Sex Ratio under Environmental Sex Determination in the Common Snapping Turtle (Chelydra Serpentina)

PubMed Central

Janzen, F. J.

1992-01-01

The magnitude of quantitative genetic variation for primary sex ratio was measured in families extracted from a natural population of the common snapping turtle (Chelydra serpentina), which possesses temperature-dependent sex determination (TSD). Eggs were incubated at three temperatures that produced mixed sex ratios. This experimental design provided estimates of the heritability of sex ratio in multiple environments and a test of the hypothesis that genotype X environment (G X E) interactions may be maintaining genetic variation for sex ratio in this population of C. serpentina. Substantial quantitative genetic variation for primary sex ratio was detected in all experimental treatments. These results in conjunction with the occurrence of TSD in this species provide support for three critical assumptions of Fisher's theory for the microevolution of sex ratio. There were statistically significant effects of family and incubation temperature on sex ratio, but no significant interaction was observed. Estimates of the genetic correlations of sex ratio across environments were highly positive and essentially indistinguishable from +1. These latter two findings suggest that G X E interaction is not the mechanism maintaining genetic variation for sex ratio in this system. Finally, although substantial heritable variation exists for primary sex ratio of C. serpentina under constant temperatures, estimates of the effective heritability of primary sex ratio in nature are approximately an order of magnitude smaller. Small effective heritability and a long generation time in C. serpentina imply that evolution of sex ratios would be slow even in response to strong selection by, among other potential agents, any rapid and/or substantial shifts in local temperatures, including those produced by changes in the global climate. PMID:1592234

Heritability and confirmation of genetic association studies for childhood asthma in twins.

PubMed

Ullemar, V; Magnusson, P K E; Lundholm, C; Zettergren, A; Melén, E; Lichtenstein, P; Almqvist, C

2016-02-01

Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ). Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intrafamilial aggregation and heritability of left ventricular geometric remodeling is independent of cardiac mass in families of African ancestry.

PubMed

Peterson, Vernice R; Norton, Gavin R; Redelinghuys, Michelle; Libhaber, Carlos D; Maseko, Muzi J; Majane, Olebogeng H I; Brooksbank, Richard; Woodiwiss, Angela J

2015-05-01

Whether left ventricular (LV) geometric remodeling, as indexed by relative wall thickness (RWT), aggregates in families and is inherited independent of LV mass (LVM) and additional confounders is uncertain. We determined whether RWT as assessed from 2D targeted M-mode echocardiography shows intrafamilial aggregation and heritability independent of LVM in 181 nuclear families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs) with 16 families including 3 generations from an urban developing community of black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E. software) were assessed independent of confounders, including central aortic systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor software). Independent of confounders including SBPc, LV RWT was correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29, P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P < 0.001) pairs persisted with further adjustments for LVM or LVM indexed to height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed significant heritability (h(2) ± SEM = 0.56 ± 0.09, P < 0.0001) and this persisted with further adjustments for LVM (h(2) ± SEM = 0.48 ± 0.09, P < 0.0001) or LVMI (h(2) ± SEM = 0.49 ± 0.09, P < 0.0001). In a group of African ancestry, independent of LVM, LV geometric remodeling shows significant intrafamilial aggregation and heritability. Genetic factors may in-part determine the LV geometric remodeling process independent of the extent of cardiac hypertrophy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic evaluation of rapid height growth in pot- and nursery-grown Scotch pine

Treesearch

Maurice E., Jr. Demeritt; Henry D. Gerhold; Henry D. Gerhold

1985-01-01

Genetic and environmental components of variance for 2-year pot and nursery heights of offspring from inter- and intraprovenance matings in Scotch pine were studied to determine which provenances and selection methods should be used in an ornamental and Christmas tree improvement program. Nursery evaluation was preferred to pot evaluation because heritability estimates...

Genetic Model Fitting in IQ, Assortative Mating & Components of IQ Variance.

ERIC Educational Resources Information Center

Capron, Christiane; Vetta, Adrian R.; Vetta, Atam

1998-01-01

The biometrical school of scientists who fit models to IQ data traces their intellectual ancestry to R. Fisher (1918), but their genetic models have no predictive value. Fisher himself was critical of the concept of heritability, because assortative mating, such as for IQ, introduces complexities into the study of a genetic trait. (SLD)

Heritability of hypothyroidism in the Finnish Hovawart population.

PubMed

Åhlgren, Johanna; Uimari, Pekka

2016-06-07

The Hovawart is a working and companion dog breed of German origin. A few hundred Hovawart dogs are registered annually in Finland. The most common disease with a proposed genetic background in Hovawarts is hypothyroidism. The disease is usually caused by lymphocytic thyroiditis, an autoimmune disorder which destroys the thyroid gland. Hypothyroidism can be treated medically with hormone replacement. Its overall incidence could also be reduced through selection, provided that the trait shows an adequate genetic basis. The aim of this study was to estimate the heritability of hypothyroidism in the Finnish Hovawart population. The pedigree data for the study were provided by the Finnish Kennel Club and the hypothyroidism data by the Finnish Hovawart Club. The data included 4953 dogs born between 1990 and 2010, of which 107 had hypothyroidism and 4846 were unaffected. Prior to the estimation of heritability, we studied the effects of gender, birth year, birth month, and inbreeding on susceptibility to hypothyroidism. Heritability was estimated with the probit model both via restricted maximum likelihood (REML) and Gibbs sampling, using litter and sire of the dog as random effects. None of the studied systematic effects or level of inbreeding had a significant effect on susceptibility to hypothyroidism. The estimated heritability of hypothyroidism varied from 0.47 (SE = 0.18) using REML to 0.62 (SD = 0.21) using Gibbs sampling. Based on our analysis, the heritability of hypothyroidism is moderate to high, suggesting that its prevalence could be decreased through selection. Thus, breeders should notify the breed association of any affected dogs, and their use for breeding should be avoided.

Do genetic factors contribute to the relation between education and metabolic risk factors in young adults? A twin study.

PubMed

Vermeiren, Angelique P A; Bosma, Hans; Gielen, Marij; Lindsey, Patrick J; Derom, Catherine; Vlietinck, Robert; Loos, Ruth J F; Zeegers, Maurice P

2013-12-01

Lower educated people have a higher prevalence of metabolic risk factors (MRF), that is, high waist circumference (WC), high systolic blood pressure, low high-density lipoprotein cholesterol level, high triglycerides and high fasting glucose levels. Behavioural and psychosocial factors cannot fully explain this educational gradient. We aim to examine the possible role of genetic factors by estimating the extent to which education and MRF share a genetic basis and the extent to which the heritability of MRF varies across educational levels. We examined 388 twin pairs, aged 18-34 years, from the Belgian East Flanders Prospective Twin Survey. Using structural equation modelling, a Cholesky bivariate model was applied to assess the shared genetic basis between education and MRF. The heritability of MRF across education levels was estimated using a non-linear multivariate Gaussian regression. Fifteen percent (P < 0.01) of the negative relation between education and WC was because of genes shared between these two traits. Furthermore, the heritability of WC was lower in the lowest educated group (65%) compared with the highest educated group (78%, P = 0.04). The lower heritabilities among the lower educated twins for the other MRF were not significant. The heritability of glucose was higher in the lowest education (80%) group compared with the high education group (67%, P = 0.01). Our findings suggest that genetic factors partly explain educational differences in WC. Furthermore, the lower heritability estimates in WC in the lower educated young adults suggest opportunities for environmental interventions to prevent the development of full-blown metabolic syndrome in middle and older age.

Lack of a heritable reproductive defect in the offspring of male rainbow trout exposed to the environmental estrogen 17α-ethynylestradiol

PubMed Central

Brown, Kim H.; Schultz, Irvin R.; Nagler, James J.

2009-01-01

Endocrine disruptors, including environmental estrogens, have been shown to induce heritable effects through both genetic and epigenetic mechanisms in mammals. Despite this information and the wealth of knowledge regarding the significant reproductive impacts endocrine disruptors impose on fishes, no studies have reported whether the observed effects are heritable. Without this information it is difficult to establish the long-term consequences for exposed populations. To determine potential consequences of long-term effects we must consider the possibility that induced reproductive defects in fishes may be heritable. Using rainbow trout (Oncorhynchus mykiss) as a model this study aims to determine whether a specific reproductive defect observed in 17α-ethynylestradiol exposed male parents, diminished progeny survival, is heritable in the unexposed surviving F1 males. Semen was collected from anesthetized males of the F1 generation upon sexual maturation at two time-points, one year old precocious males and two years old males. In vitro fertilization was used to produce an F2 generation. F2 embryos were then analyzed for survival at 19 days post-fertilization (eye pigmentation) and the different treatment groups statistically compared to the controls. Analysis indicated that F2 offspring survival from F1 males propagated from both exposed and unexposed parents survive normally and no heritable effect was observed in males from the F1 generation for this specific reproductive defect. These results provide scope for the recovery of fish populations exposed to environmental estrogens should the contaminant be removed. PMID:19036459

Estimation of heritability, evolvability and genetic correlations of two pollen and pistil traits involved in a sexual conflict over timing of stigma receptivity in Collinsia heterophylla (Plantaginaceae).

PubMed

Madjidian, Josefin A; Andersson, Stefan; Lankinen, Asa

2012-07-01

Heritable genetic variation is crucial for selection to operate, yet there is a paucity of studies quantifying such variation in interactive male/female sexual traits, especially those of plants. Previous work on the annual plant Collinsia heterophylla, a mixed-mating species, suggests that delayed stigma receptivity is involved in a sexual conflict: pollen from certain donors fertilize ovules earlier than others at the expense of reduced maternal seed set and lower levels of pollen competition. Parent-offspring regressions and sib analyses were performed to test for heritable genetic variation and co-variation in male and female interactive traits related to the sexual conflict. SOME heritable variation and evolvability were found for the female trait (delayed stigma receptivity in presence of pollen), but no evidence was found for genetic variation in the male trait (ability to fertilize ovules early). The results further indicated a marginally significant correlation between a male's ability to fertilize early and early stigma receptivity in offspring. However, despite potential indirect selection of these traits, antagonistic co-evolution may not occur given the lack of heritability of the male trait. To our knowledge, this is the first study of a plant or any hermaphrodite that examines patterns of genetic correlation between two interactive sexual traits, and also the first to assess heritabilities of plant traits putatively involved in a sexual conflict. It is concluded that the ability to delay fertilization in presence of pollen can respond to selection, while the pollen trait has lower evolutionary potential.

Heritability and linkage analysis of personality in bipolar disorder.

PubMed

Greenwood, Tiffany A; Badner, Judith A; Byerley, William; Keck, Paul E; McElroy, Susan L; Remick, Ronald A; Dessa Sadovnick, A; Kelsoe, John R

2013-11-01

The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST). We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available. Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12). The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study. While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility. © 2013 Elsevier B.V. All rights reserved.

Heritability of hunger relationships with food intake in free-living humans.

PubMed

De Castro, J M

1999-08-01

The heritability of the before and after meal self-ratings of hunger and thirst and their relationship to food intake was investigated with 110 identical and 102 fraternal same-sex and 53 fraternal mixed-gender adult twin pairs who were paid to maintain 7-day food intake diaries. From the diary reports, the total and meal intakes of food energy and the amounts of the macronutrients ingested were estimated. Subjects rated their subjective levels of hunger on a seven-point scale both before and after eating. Linear structural modeling was applied to investigate the nature and degree of genetic and environmental influences and revealed significant genetic influences on the self-rated levels of hunger both before and after the meals and the change in hunger over the meal. In addition, the relationship between hunger and intake was influenced by the genes. Significant heritabilities were found for the correlations, and the slopes of the regression lines relating before-meal hunger to meal size and also the change in hunger over the meal to intake. This indicates that hunger's effect on intake and, in turn, intake's effects on hunger are to some extent heritable. This suggests that the level of subjective experience and the individuals responses to them are influenced by the genes and become part of the total package of genetically determined physiological, socio/cultural, and psychological processes that regulate energy balance.

Genetic covariance between central corneal thickness and anterior chamber volume: a Hungarian twin study.

PubMed

Toth, Georgina Zsofia; Racz, Adel; Tarnoki, Adam Domonkos; Tarnoki, David Laszlo; Szekelyhidi, Zita; Littvay, Levente; Suveges, Ildiko; Nemeth, Janos; Nagy, Zoltan Zsolt

2014-10-01

Few, and inconsistent, studies have showed high heritability of some parameters of the anterior segment of the eye; however, no heritability of anterior chamber volume (ACV) has been reported, and no study has been performed to investigate the correlation between the ACV and central corneal thickness (CCT). Anterior segment measurements (Pentacam, Oculus) were obtained from 220 eyes of 110 adult Hungarian twins (41 monozygotic and 14 same-sex dizygotic pairs; 80% women; age 48.6 ± 15.5 years) obtained from the Hungarian Twin Registry. Age- and sex-adjusted heritability of ACV was 85% (bootstrapped 95% confidence interval; CI: 69% to 93%), and 88% for CCT (CI: 79% to 95%). Common environmental effects had no influence, and unshared environmental factors were responsible for 12% and 15% of the variance, respectively. The correlation between ACV and CCT was negative and significant (r ph = -0.35, p < .05), and genetic factors accounted for the covariance significantly (0.934; CI: 0.418, 1.061) based on the bivariate Cholesky decomposition model. These findings support the high heritability of ACV and central corneal thickness, and a strong genetic covariance between them, which underscores the importance of identification of the specific genetic factors and the family risk-based screening of disorders related to these variables, such as open-angle and also angle closure glaucoma and corneal endothelial alterations.

Environmental and genetic factors affecting milk yield and quality in three Italian sheep breeds.

PubMed

Selvaggi, Maria; D'Alessandro, Angela Gabriella; Dario, Cataldo

2017-02-01

The aims of the study described in the Research Communication were to determine the level of influence of some environmental factors on milk yield and quality traits, including lactose, and lactation length in ewes belonging to three different Italian breeds and to estimate the heritability for the same traits. A total of 2138 lactation records obtained from 535 ewes belonging to three different Italian breeds (Comisana, Leccese, and Sarda) were used. Breed significantly affected all of the considered traits. Moreover, year of lambing affected milk yield and lactation length without influence on milk quality traits. Parity affected significantly only the milk yield, whereas type of birth showed its effect on milk yield, fat, protein, and lactose yield. On the whole, the presently reported heritability estimates are within the range of those already obtained in other dairy breeds by other authors, with values for lactation length being very low in all the investigated populations. Considering the heritability estimates for lactose content and yield, to the best of our knowledge, there is a lack of information on these parameters in ovine species and this is the first report on heritability of lactose content and yield in dairy sheep breeds. Our results suggest that genetic variability for milk traits other than lactation length is adequate for selection indicating a good response to selection in these breeds.

Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

PubMed

Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

2012-03-01

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie.

PubMed

De Risio, Luisa; Lewis, Tom; Freeman, Julia; de Stefani, Alberta; Matiasek, Lara; Blott, Sarah

2011-06-01

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gender and genetic contributions to weight identity among adolescents and young adults in the U.S.

PubMed

Wedow, Robbee; Briley, Daniel A; Short, Susan E; Boardman, Jason D

2016-09-01

In this paper, we investigate the possibility that genetic variation contributes to self-perceived weight status among adolescents and young adults in the U.S. Using samples of identical and fraternal twins across four waves of the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, we calculate heritability estimates for objective body mass index (BMI) that are in line with previous estimates. We also show that perceived weight status is heritable (h(2) ∼ 0.47) and most importantly that this trait continues to be heritable above and beyond objective BMI (h(2) ∼ 0.25). We then demonstrate significant sex differences in the heritability of weight identity across the four waves of the study, where h(2)women = 0.39, 0.35, 0.40, and 0.50 for each wave, respectively, and h(2)men = 0.10, 0.10, 0.23, and 0.03. These results call for a deeper consideration of both identity and gender in genetics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

PubMed

Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb; Pomerantz, Mark; Li, Fugen; Long, Henry W; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Zheng, Wei; Pettaway, Curtis A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; John, Esther M; Murphy, Adam B; Signorello, Lisa B; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anslem J M; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Witte, John S; Casey, Graham; Kaggwa, Sam; Cook, Michael B; Stram, Daniel O; Blot, William J; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Teerlink, Craig; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Sellers, Thomas A; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Teixeira, Manuel R; Pandha, Hardev; Michael, Agnieszka; Paulo, Paula; Maia, Sofia; Kierzek, Andrzej; Conti, David V; Albanes, Demetrius; Berg, Christine; Berndt, Sonja I; Campa, Daniele; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Gaziano, J Michael; Giovannucci, Edward; Hoover, Robert; Hunter, David J; Johansson, Mattias; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Navarro, Carmen; Overvad, Kim; Riboli, Elio; Siddiq, Afshan; Stevens, Victoria L; Trichopoulos, Dimitrios; Vineis, Paolo; Yeager, Meredith; Trynka, Gosia; Raychaudhuri, Soumya; Schumacher, Frederick R; Price, Alkes L; Freedman, Matthew L; Haiman, Christopher A; Pasaniuc, Bogdan

2016-04-07

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Sleep Reactivity and Insomnia: Genetic and Environmental Influences

PubMed Central

Drake, Christopher L.; Friedman, Naomi P.; Wright, Kenneth P.; Roth, Thomas

2011-01-01

Study Objectives: Determine the genetic and environmental contributions to sleep reactivity and insomnia. Design: Population-based twin cohort. Participants: 1782 individual twins (988 monozygotic or MZ; 1,086 dizygotic or DZ), including 744 complete twin pairs (377 MZ and 367 DZ). Mean age was 22.5 ± 2.8 years; gender distribution was 59% women. Measurements: Sleep reactivity was measured using the Ford Insomnia Response to Stress Test (FIRST). The criterion for insomnia was having difficulty falling asleep, staying asleep, or nonrefreshing sleep “usually or always” for ≥ 1 month, with at least “somewhat” interference with daily functioning. Results: The prevalence of insomnia was 21%. Heritability estimates for sleep reactivity were 29% for females and 43% for males. The environmental variance for sleep reactivity was greater for females and entirely due to nonshared effects. Insomnia was 43% to 55% heritable for males and females, respectively; the sex difference was not significant. The genetic variances in insomnia and FIRST scores were correlated (r = 0.54 in females, r = 0.64 in males), as were the environmental variances (r = 0.32 in females, r = 0.37 in males). In terms of individual insomnia symptoms, difficulty staying asleep (25% to 35%) and nonrefreshing sleep (34% to 35%) showed relatively more genetic influences than difficulty falling asleep (0%). Conclusions: Sleep reactivity to stress has a substantial genetic component, as well as an environmental component. The finding that FIRST scores and insomnia symptoms share genetic influences is consistent with the hypothesis that sleep reactivity may be a genetic vulnerability for developing insomnia. Citation: Drake CL; Friedman NP; Wright KP; Roth T. Sleep reactivity and insomnia: genetic and environmental influences. SLEEP 2011;34(9):1179-1188. PMID:21886355

The genetic basis of female multiple mating in a polyandrous livebearing fish

PubMed Central

Evans, Jonathan P; Gasparini, Clelia

2013-01-01

The widespread occurrence of female multiple mating (FMM) demands evolutionary explanation, particularly in the light of the costs of mating. One explanation encapsulated by “good sperm” and “sexy-sperm” (GS-SS) theoretical models is that FMM facilitates sperm competition, thus ensuring paternity by males that pass on genes for elevated sperm competitiveness to their male offspring. While support for this component of GS-SS theory is accumulating, a second but poorly tested assumption of these models is that there should be corresponding heritable genetic variation in FMM – the proposed mechanism of postcopulatory preferences underlying GS-SS models. Here, we conduct quantitative genetic analyses on paternal half-siblings to test this component of GS-SS theory in the guppy (Poecilia reticulata), a freshwater fish with some of the highest known rates of FMM in vertebrates. As with most previous quantitative genetic analyses of FMM in other species, our results reveal high levels of phenotypic variation in this trait and a correspondingly low narrow-sense heritability (h2 = 0.11). Furthermore, although our analysis of additive genetic variance in FMM was not statistically significant (probably owing to limited statistical power), the ensuing estimate of mean-standardized additive genetic variance (IA = 0.7) was nevertheless relatively low compared with estimates published for life-history traits across a broad range of taxa. Our results therefore add to a growing body of evidence that FMM is characterized by relatively low additive genetic variation, thus apparently contradicting GS-SS theory. However, we qualify this conclusion by drawing attention to potential deficiencies in most designs (including ours) that have tested for genetic variation in FMM, particularly those that fail to account for intersexual interactions that underlie FMM in many systems. PMID:23403856

Genetic Architecture of Ear Fasciation in Maize (Zea mays) under QTL Scrutiny

PubMed Central

Mendes-Moreira, Pedro; Alves, Mara L.; Satovic, Zlatko; dos Santos, João Pacheco; Santos, João Nina; Souza, João Cândido; Pêgo, Silas E.; Hallauer, Arnel R.; Vaz Patto, Maria Carlota

2015-01-01

Maize ear fasciation Knowledge of the genes affecting maize ear inflorescence may lead to better grain yield modeling. Maize ear fasciation, defined as abnormal flattened ears with high kernel row number, is a quantitative trait widely present in Portuguese maize landraces. Material and Methods Using a segregating population derived from an ear fasciation contrasting cross (consisting of 149 F2:3 families) we established a two location field trial using a complete randomized block design. Correlations and heritabilities for several ear fasciation-related traits and yield were determined. Quantitative Trait Loci (QTL) involved in the inheritance of those traits were identified and candidate genes for these QTL proposed. Results and Discussion Ear fasciation broad-sense heritability was 0.73. Highly significant correlations were found between ear fasciation and some ear and cob diameters and row number traits. For the 23 yield and ear fasciation-related traits, 65 QTL were identified, out of which 11 were detected in both environments, while for the three principal components, five to six QTL were detected per environment. Detected QTL were distributed across 17 genomic regions and explained individually, 8.7% to 22.4% of the individual traits or principal components phenotypic variance. Several candidate genes for these QTL regions were proposed, such as bearded-ear1, branched silkless1, compact plant1, ramosa2, ramosa3, tasselseed4 and terminal ear1. However, many QTL mapped to regions without known candidate genes, indicating potential chromosomal regions not yet targeted for maize ear traits selection. Conclusions Portuguese maize germplasm represents a valuable source of genes or allelic variants for yield improvement and elucidation of the genetic basis of ear fasciation traits. Future studies should focus on fine mapping of the identified genomic regions with the aim of map-based cloning. PMID:25923975

Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22

PubMed Central

Pulli, K; Karma, K; Norio, R; Sistonen, P; Göring, H H H; Järvelä, I

2008-01-01

Background: Music perception and performance are comprehensive human cognitive functions and thus provide an excellent model system for studying human behaviour and brain function. However, the molecules involved in mediating music perception and performance are so far uncharacterised. Objective: To unravel the biological background of music perception, using molecular and statistical genetic approaches. Methods: 15 Finnish multigenerational families (with a total of 234 family members) were recruited via a nationwide search. The phenotype of all family members was determined using three tests used in defining musical aptitude: a test for auditory structuring ability (Karma Music test; KMT) commonly used in Finland, and the Seashore pitch and time discrimination subtests (SP and ST respectively) used internationally. We calculated heritabilities and performed a genome-wide variance components-based linkage scan using genotype data for 1113 microsatellite markers. Results: The heritability estimates were 42% for KMT, 57% for SP, 21% for ST and 48% for the combined music test scores. Significant evidence of linkage was obtained on chromosome 4q22 (LOD 3.33) and suggestive evidence of linkage at 8q13-21 (LOD 2.29) with the combined music test scores, using variance component linkage analyses. The major contribution of the 4q22 locus was obtained for the KMT (LOD 2.91). Interestingly, a positive LOD score of 1.69 was shown at 18q, a region previously linked to dyslexia (DYX6) using combined music test scores. Conclusion: Our results show that there is a genetic contribution to musical aptitude that is likely to be regulated by several predisposing genes or variants. PMID:18424507

Genetic Architecture of Ear Fasciation in Maize (Zea mays) under QTL Scrutiny.

PubMed

Mendes-Moreira, Pedro; Alves, Mara L; Satovic, Zlatko; Dos Santos, João Pacheco; Santos, João Nina; Souza, João Cândido; Pêgo, Silas E; Hallauer, Arnel R; Vaz Patto, Maria Carlota

2015-01-01

Knowledge of the genes affecting maize ear inflorescence may lead to better grain yield modeling. Maize ear fasciation, defined as abnormal flattened ears with high kernel row number, is a quantitative trait widely present in Portuguese maize landraces. Using a segregating population derived from an ear fasciation contrasting cross (consisting of 149 F2:3 families) we established a two location field trial using a complete randomized block design. Correlations and heritabilities for several ear fasciation-related traits and yield were determined. Quantitative Trait Loci (QTL) involved in the inheritance of those traits were identified and candidate genes for these QTL proposed. Ear fasciation broad-sense heritability was 0.73. Highly significant correlations were found between ear fasciation and some ear and cob diameters and row number traits. For the 23 yield and ear fasciation-related traits, 65 QTL were identified, out of which 11 were detected in both environments, while for the three principal components, five to six QTL were detected per environment. Detected QTL were distributed across 17 genomic regions and explained individually, 8.7% to 22.4% of the individual traits or principal components phenotypic variance. Several candidate genes for these QTL regions were proposed, such as bearded-ear1, branched silkless1, compact plant1, ramosa2, ramosa3, tasselseed4 and terminal ear1. However, many QTL mapped to regions without known candidate genes, indicating potential chromosomal regions not yet targeted for maize ear traits selection. Portuguese maize germplasm represents a valuable source of genes or allelic variants for yield improvement and elucidation of the genetic basis of ear fasciation traits. Future studies should focus on fine mapping of the identified genomic regions with the aim of map-based cloning.

Internet addiction and its facets: The role of genetics and the relation to self-directedness.

PubMed

Hahn, Elisabeth; Reuter, Martin; Spinath, Frank M; Montag, Christian

2017-02-01

A growing body of research focuses on problematic behavior patterns related to the use of the Internet to identify contextual as well as individual risk factors of this new phenomenon called Internet addiction (IA). IA can be described as a multidimensional syndrome comprising aspects such as craving, development of tolerance, loss of control and negative consequences. Given that previous research on other addictive behaviors showed substantial heritability, it can be expected that the vulnerability to IA may also be due to a person's genetic predisposition. However, it is questionable whether distinct components of IA have different etiologies. Using data from a sample of adult monozygotic and dizygotic twins and non-twin siblings (N=784 individuals, N=355 complete pairs, M=30.30years), we investigated the magnitude of genetic and environmental influences on generalized IA as well as on specific facets such as excessive use, self-regulation, preference for online social interaction or negative consequences. To explain the heritability in IA, we further examined the relation to Self-Directedness as potential mediating source. Results showed that relative contributions of genetic influences vary considerable for different components of IA. For generalized IA factors, individual differences could be explained by shared and non-shared environmental influences while genetic influences did not play a role. For specific facets of IA and private Internet use in hours per week, heritability estimates ranged between 21% and 44%. Bivariate analysis indicated that Self-Directedness accounted for 20% to 65% of the genetic variance in specific IA facets through overlapping genetic pathways. Implications for future research are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency.

PubMed

Lopez, Gerardo; Pallas, Benoît; Martinez, Sébastien; Lauri, Pierre-Éric; Regnard, Jean-Luc; Durel, Charles-Éric; Costes, Evelyne

2015-01-01

Water use efficiency (WUE) is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration) in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76) and WUE (0.73) were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water.

Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency

PubMed Central

Lopez, Gerardo; Pallas, Benoît; Martinez, Sébastien; Lauri, Pierre-Éric; Regnard, Jean-Luc; Durel, Charles-Éric; Costes, Evelyne

2015-01-01

Water use efficiency (WUE) is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration) in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76) and WUE (0.73) were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water. PMID:26717192

Heritability and social brood effects on personality in juvenile and adult life-history stages in a wild passerine.

PubMed

Winney, I S; Schroeder, J; Nakagawa, S; Hsu, Y-H; Simons, M J P; Sánchez-Tójar, A; Mannarelli, M-E; Burke, T

2018-01-01

How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype or because our concept of personality and the stability of behaviour needs to be revised. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

The contribution of genetics and early rearing experiences to hierarchical personality dimensions in chimpanzees (Pan troglodytes).

PubMed

Latzman, Robert D; Freeman, Hani D; Schapiro, Steven J; Hopkins, William D

2015-11-01

A reliable literature finds that traits are related to each other in an organized hierarchy encompassing various conceptualizations of personality (e.g., Big Three, five-factor model). Recent work suggests the potential of a similar organization among our closest nonhuman relative, chimpanzees (Pan troglodytes), with significant links to neurobiology suggesting an evolutionarily and neurobiologically based hierarchical structure of personality. The current study investigated this hierarchical structure, the heritability of the various personality dimensions across levels of the hierarchy, and associations with early social rearing experience in a large sample (N = 238) of socially housed, captive chimpanzees residing in 2 independent colonies of apes. Results provide support for a hierarchical structure of personality in chimpanzees with significant associations with early rearing experiences. Further, heritabilities of the various dimensions varied by early rearing, with affective dimensions found to be significantly heritable among mother-reared apes, whereas personality dimensions were largely independent of relatedness among the nursery-reared apes. Taken together, these findings provide evidence for the influence of both genetic and environmental factors on personality profiles across levels of the hierarchy, supporting the importance of considering environmental variation in models of quantitative trait evolution. (c) 2015 APA, all rights reserved).

Genetic basis in motor skill and hand preference for tool use in chimpanzees (Pan troglodytes).

PubMed

Hopkins, William D; Reamer, Lisa; Mareno, Mary Catherine; Schapiro, Steven J

2015-02-07

Chimpanzees are well known for their tool using abilities. Numerous studies have documented variability in tool use among chimpanzees and the role that social learning and other factors play in their development. There are also findings on hand use in both captive and wild chimpanzees; however, less understood are the potential roles of genetic and non-genetic mechanisms in determining individual differences in tool use skill and laterality. Here, we examined heritability in tool use skill and handedness for a probing task in a sample of 243 captive chimpanzees. Quantitative genetic analysis, based on the extant pedigrees, showed that overall both tool use skill and handedness were significantly heritable. Significant heritability in motor skill was evident in two genetically distinct populations of apes, and between two cohorts that received different early social rearing experiences. We further found that motor skill decreased with age and that males were more commonly left-handed than females. Collectively, these data suggest that though non-genetic factors do influence tool use performance and handedness in chimpanzees, genetic factors also play a significant role, as has been reported in humans. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The contribution of genetics and early rearing experiences to hierarchical personality dimensions in chimpanzees (Pan troglodytes)

PubMed Central

Latzman, Robert D.; Freeman, Hani D.; Schapiro, Steven J.; Hopkins, William D.

2015-01-01

A reliable literature finds that traits are related to each other in an organized hierarchy encompassing various conceptualizations of personality (e.g., Big Three, Five Factor Model). Recent work suggests the potential of a similar organization among our closest nonhuman relative, chimpanzees (Pan troglodytes), with significant links to neurobiology suggesting an evolutionarily- and neurobiologically-based hierarchical structure of personality. The current study investigated this hierarchical structure, the heritability of the various personality dimensions across levels of the hierarchy, and associations with early social rearing experience in a large sample (N = 238) of socially-housed, captive chimpanzees residing in two independent colonies of apes. Results provide support for a hierarchical structure of personality in chimpanzees with significant associations with early rearing experiences. Further, heritabilities of the various dimensions varied by early rearing, with affective dimensions found to be significantly heritable among mother-reared apes, while personality dimensions were largely independent of relatedness among the nursery-reared apes. Taken together, these findings provide evidence for the influence of both genetic and environmental factors on personality profiles across levels of the hierarchy, supporting the importance of considering environmental variation in models of quantitative trait evolution. PMID:25915132

Heritability of and strong single gene (Pgi) effects on life-history traits in the Glanville fritillary butterfly.

PubMed

Klemme, I; Hanski, I

2009-09-01

We estimated broad-sense heritabilities (H(2)) of 13 female and seven male life-history traits of the Glanville fritillary butterfly (Melitaea cinxia) under semi-natural conditions in a large outdoor population cage. The analysis was based on full-sib families collected as young larvae in the field and reared under common garden conditions. We found significant genetic variance in female lifespan, fecundity, number of matings and host-plant preference as well as in male body mass and mobility. Apart from host-plant preference, female traits that were more strongly correlated with lifetime reproductive success (LRS; measured as total number of eggs laid) had higher H(2). LRS itself exhibited significant heritability. Host-plant preference had very high H(2), consistent with a previously reported genetically determined geographical cline in host-plant preference in the study area. Lifespan and egg hatching rate were significantly associated with a SNP in the coding region of the Pgi gene, for which there is previous evidence for balancing selection. Selection on Pgi, which furthermore shows spatial and temporal variation, may maintain genetic variance in fitness-related life-history traits. In contrast, we found no strong evidence for life-history trade-offs.

Relationship between genetic parameters in maize (Zea mays) with seedling growth parameters under 40-100% soil moisture conditions.

PubMed

Muhammad, R W; Qayyum, A

2013-10-18

We estimated the association of genetic parameters with production characters in 64 maize (Zea mays) genotypes in a green house in soil with 40-100% moisture levels (percent of soil moisture capacity). To identify the major parameters that account for variation among the genotypes, we used single linkage cluster analysis and principle component analysis. Ten plant characters were measured. The first two, four, three, and again three components, with eigen values > 1 contributed 75.05, 80.11, 68.67, and 75.87% of the variability among the genotypes under the different moisture levels, i.e., 40, 60, 80, and 100%, respectively. Other principal components (3-10, 5-10, and 4-10) had eigen values less than 1. The highest estimates of heritability were found for root fresh weight, root volume (0.99), and shoot fresh weight (0.995) in 40% soil moisture. Values of genetic advance ranged from 23.4024 for SR at 40% soil moisture to 0.2538 for shoot dry weight in 60% soil moisture. The high magnitude of broad sense heritability provides evidence that these plant characters are under the control of additive genetic effects. This indicates that selection should lead to fast genetic improvement of the material. The superior agronomic types that we identified may be exploited for genetic potential to improve yield potential of the maize crop.

Population parameters for resistance to Fusarium graminearum and Fusarium verticillioides ear rot among large sets of early, mid-late and late maturing European maize (Zea mays L.) inbred lines.

PubMed

Löffler, Martin; Kessel, Bettina; Ouzunova, Milena; Miedaner, Thomas

2010-03-01

Infection of maize ears with Fusarium graminearum (FG) and Fusarium verticillioides (FV) reduces yield and quality by mycotoxin contamination. Breeding and growing varieties resistant to both Fusarium spp. is the best alternative to minimize problems. The objectives of our study were to draw conclusions on breeding for ear rot resistance by estimating variance components, heritabilities and correlations between resistances to FV and FG severity and to investigate different inoculation methods. In 2007 and 2008, three maturity groups (early, mid-late, late) each comprising about 150 inbred lines were tested in Germany, France, Italy, and Hungary according to their maturity group. They were silk channel inoculated by FG (early) and FV (all groups). In the late maturity group, additionally kernel inoculation was applied in a separate trial. The percentage of mycelium coverage on the ear was rated at harvest (0-100%). Significant (P < 0.01) genotypic variances of ear rot severity were found in all groups. Inoculation was superior to natural infection because of higher disease severities and heritabilities. In early maturing flints and dents, FG caused significantly (P < 0.01) higher ear rot severity than FV (61.7 and 55.1% FG vs. 18.2 and 11.1% FV ear rot severity, respectively). FV inoculation in Southern Europe (mid-late, late) resulted in similar means between 10.3 and 14.0%. Selection is complicated by significant (P < 0.01) genotype x environment interactions. Correlation between FG and FV severity was moderate in flints and dents (r = 0.59 and 0.49, respectively) but lines resistant to both fungi exist. We conclude that chances for selecting improved European elite maize material within the existing germplasms is promising by multi-environmental inoculation trials.

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

PubMed

Lee, Miryoung; Czerwinski, Stefan A; Choh, Audrey C; Demerath, Ellen W; Sun, Shumei S; Chumlea, Wm C; Towne, Bradford; Siervogel, Roger M

2006-03-01

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample

ERIC Educational Resources Information Center

Mathews, Carol A.; Grados, Marco A.

2011-01-01

Objective: Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among TS,…

Height and diameter variation in twelve white ash provenance/progeny tests in eastern United States

Treesearch

G. Rink; F.H. Kung

1991-01-01

Results from 12- and 13-year old rangewide provenance/progeny tests of white ash (Fraxinus americana L.) planted at 12 locations throughout the eastern United States are reported. Although heritability of white ash tree height and dbh is high at both the provenance and family levels, the trend in variance components is for increasing provenance and...

Heritability of climate-relevant traits in a rainforest skink.

PubMed

Martins, Felipe; Kruuk, Loeske; Llewelyn, John; Moritz, Craig; Phillips, Ben

2018-05-22

There is justified concern about the impact of global warming on the persistence of tropical ectotherms. There is also growing evidence for strong selection on climate-relevant physiological traits. Understanding the evolutionary potential of populations is especially important for low dispersal organisms in isolated populations, because these populations have little choice but to adapt. Despite this, direct estimates of heritability and genetic correlations for physiological traits in ectotherms-which will determine their evolutionary responses to selection-are sparse, especially for reptiles. Here we examine the heritabilities and genetic correlations for a set of four morphological and six climate-relevant physiological traits in an isolated population of an Australian rainforest lizard, Lampropholis coggeri. These traits show considerable variation across populations in this species, suggesting local adaptation. From laboratory crosses, we estimated very low to moderate heritability of temperature-related physiological traits (h 2  < 0.31), but significant and higher heritability of desiccation resistance (h 2 ~0.42). These values contrasted with uniformly higher heritabilities (h 2  > 0.51) for morphological traits. At the phenotypic level, there were positive associations among the morphological traits and between thermal limits. Growth rate was positively correlated with thermal limits, but there was no indication that morphology and physiology were linked in any other way. We found some support for a specialist-generalist trade-off in the thermal performance curve, but otherwise there was no evidence for evolutionary constraints, suggesting broadly labile multivariate trait structure. Our results indicate little potential to respond to selection on thermal traits in this population and provide new insights into the capacity of tropical ectotherms to adapt in situ to rapid climate change.

Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population.

PubMed

Dai, Juncheng; Shen, Wei; Wen, Wanqing; Chang, Jiang; Wang, Tongmin; Chen, Haitao; Jin, Guangfu; Ma, Hongxia; Wu, Chen; Li, Lian; Song, Fengju; Zeng, YiXin; Jiang, Yue; Chen, Jiaping; Wang, Cheng; Zhu, Meng; Zhou, Wen; Du, Jiangbo; Xiang, Yongbing; Shu, Xiao-Ou; Hu, Zhibin; Zhou, Weiping; Chen, Kexin; Xu, Jianfeng; Jia, Weihua; Lin, Dongxin; Zheng, Wei; Shen, Hongbing

2017-01-15

The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWASs) have identified a number of common single-nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (LC) (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for hepatitis B virus-related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250 kb or 500 kb upward and downward of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for LC (R 2  = 0.641, p = 0.001) and esophageal squamous cell cancer (R 2  = 0.633, p = 0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese. © 2016 UICC.

Parenting behaviour is highly heritable in male stickleback

PubMed Central

Trapp, Rebecca

2018-01-01

Parental care is critical for fitness, yet little is known about its genetic basis. Here, we estimate the heritability of parenting behaviour in a species famous for its diversity and its behavioural repertoire: three-spined stickleback (Gasterosteus aculeatus). Male three-spined stickleback are the sole providers of parental care that is necessary for offspring survival; therefore, this system offers the opportunity to study the inheritance of parental behaviour when selection is primarily acting on males. Fanning behaviour is a conspicuous parental behaviour that is readily quantified in this species. We show that the heritability of fanning behaviour is ≥0.9 and significantly different from zero within a freshwater population. Moreover, there was abundant genetic variation for fanning behaviour, indicating that it could readily evolve. These results suggest that parenting behaviour is tractable for further genetic dissection in this system. PMID:29410816

Heritability in the genomics era--concepts and misconceptions.

PubMed

Visscher, Peter M; Hill, William G; Wray, Naomi R

2008-04-01

Heritability allows a comparison of the relative importance of genes and environment to the variation of traits within and across populations. The concept of heritability and its definition as an estimable, dimensionless population parameter was introduced by Sewall Wright and Ronald Fisher nearly a century ago. Despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine. Recent reports of substantial heritability for gene expression and new estimation methods using marker data highlight the relevance of heritability in the genomics era.

Does rapid evolution matter? Measuring the rate of contemporary evolution and its impacts on ecological dynamics.

PubMed

Ellner, Stephen P; Geber, Monica A; Hairston, Nelson G

2011-06-01

Rapid contemporary evolution due to natural selection is common in the wild, but it remains uncertain whether its effects are an essential component of community and ecosystem structure and function. Previously we showed how to partition change in a population, community or ecosystem property into contributions from environmental and trait change, when trait change is entirely caused by evolution (Hairston et al. 2005). However, when substantial non-heritable trait change occurs (e.g. due to phenotypic plasticity or change in population structure) that approach can mis-estimate both contributions. Here, we demonstrate how to disentangle ecological impacts of evolution vs. non-heritable trait change by combining our previous approach with the Price Equation. This yields a three-way partitioning into effects of evolution, non-heritable phenotypic change and environment. We extend the approach to cases where ecological consequences of trait change are mediated through interspecific interactions. We analyse empirical examples involving fish, birds and zooplankton, finding that the proportional contribution of rapid evolution varies widely (even among different ecological properties affected by the same trait), and that rapid evolution can be important when it acts to oppose and mitigate phenotypic effects of environmental change. Paradoxically, rapid evolution may be most important when it is least evident. © 2011 Blackwell Publishing Ltd/CNRS.

Estimation of genetic parameters and detection of quantitative trait loci for minerals in Danish Holstein and Danish Jersey milk.

PubMed

Buitenhuis, Bart; Poulsen, Nina A; Larsen, Lotte B; Sehested, Jakob

2015-05-21

Bovine milk provides important minerals, essential for human nutrition and dairy product quality. For changing the mineral composition of the milk to improve dietary needs in human nutrition and technological properties of milk, a thorough understanding of the genetics underlying milk mineral contents is important. Therefore the aim of this study was to 1) estimate the genetic parameters for individual minerals in Danish Holstein (DH) (n=371) and Danish Jersey (DJ) (n=321) milk, and 2) detect genomic regions associated with mineral content in the milk using a genome-wide association study (GWAS) approach. For DH, high heritabilities were found for Ca (0.72), Zn (0.49), and P (0.46), while for DJ, high heritabilities were found for Ca (0.63), Zn (0.57), and Mg (0.57). Furthermore, intermediate heritabilities were found for Cu in DH, and for K, Na, P and Se in the DJ. The GWAS revealed a total of 649 significant SNP markers detected for Ca (24), Cu (90), Fe (111), Mn (3), Na (1), P (4), Se (12) and Zn (404) in DH, while for DJ, a total of 787 significant SNP markers were detected for Ca (44), Fe (43), K (498), Na (4), Mg (1), P (94) and Zn (3). Comparing the list of significant markers between DH and DJ revealed that the SNP ARS-BFGL-NGS-4939 was common in both breeds for Zn. This SNP marker is closely linked to the DGAT1 gene. Even though we found significant SNP markers on BTA14 in both DH and DJ for Ca, and Fe these significant SNPs did not overlap. The results show that Ca, Zn, P and Mg show high heritabilities. In combination with the GWAS results this opens up possibilities to select for specific minerals in bovine milk.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia

PubMed Central

Lee, Phil H.; Baker, Justin T.; Holmes, Avram J.; Jahanshad, Neda; Ge, Tian; Jung, Jae-Yoon; Cruz, Yanela; Manoach, Dara S.; Hibar, Derrek P.; Faskowitz, Joshua; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicolas H.; Wright, Margaret J.; Öngür, Dost; Buckner, Randy; Roffman, Joshua; Thompson, Paul M.; Smoller, Jordan W.

2016-01-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide SNP and neuroimaging data from 1,750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (FDR=10%). In particular, intracranial volume (ICV) and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder. PMID:27725656

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

PubMed

Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W

2016-12-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Shared genetic factors underlie migraine and depression

PubMed Central

Yang, Yuanhao; Zhao, Huiying; Heath, Andrew C; Madden, Pamela AF; Martin, Nicholas G; Nyholt, Dale R

2017-01-01

Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterise the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine™ screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53–60%) and 42% (95% CI: 37–46%), respectively. A significant additive genetic correlation (rG=0.36, 95% CI: 0.29–0.43) and bivariate heritability (h2=5.5%, 95% CI: 3.6–7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h2 (13.3%, 95% CI: 7.0–24.5%) and rG (0.51, 95% CI: 0.37–0.69) estimates significantly increased when analysing the more narrow clinically-accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms. PMID:27302564

Heritability of body weight and resistance to ammonia in the Pacific white shrimp Litopenaeus vannamei juveniles

NASA Astrophysics Data System (ADS)

Li, Wenjia; Lu, Xia; Luan, Sheng; Luo, Kun; Sui, Juan; Kong, Jie

2016-09-01

Ammonia, toxic to aquaculture organisms, represents a potential problem in aquaculture systems, and the situation is exacerbated in closed and intensive shrimp farming operations, expecially for Litopenaeus vannamei. Assessing the potential for the genetic improvement of resistance to ammonia in L. vannamei requires knowledge of the genetic parameters of this trait. The heritability of resistance to ammonia was estimated using two descriptors in the present study: the survival time (ST) and the survival status at half lethal time (SS50) for each individual under high ammonia challenge. The heritability of ST and SS50 were low (0.154 4±0.044 6 and 0.147 5±0.040 0, respectively), but they were both significantly different from zero ( P<0.01). Moreover, these two estimates were basically the same and showed no significant differences from each other ( P>0.05), suggesting that ST and SS50 could be used as suitable indicators for resistance to ammonia. There were also positive phenotypic and genetic correlation between resistance to ammonia and body weight, which means that resistance to ammonia can be enhanced by the improvement of husbandry practices that increase the body weight. The results from the present study suggest that the selection for higher body weight does not have any negative consequences for resistance to ammonia. In addition to quantitative genetics, tools from molecular genetics can be applied to selective breeding programs to improve the efficiency of selection for traits with low heritability.

The genetics of cholesteatoma. A systematic review using narrative synthesis.

PubMed

Jennings, B A; Prinsley, P; Philpott, C; Willis, G; Bhutta, M F

2018-02-01

A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale, up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology. A systematic search of MEDLINE (EBSCO) and two databases of curated genetic research (OMIM and Phenopedia) was conducted. The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants. The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis. A narrative synthesis was conducted, and data were tabulated to record characteristics, including study design, genetic data and author conclusions. Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case reports, congenital and acquired cholesteatomas have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation. This is the first systematic review about the genetics of cholesteatoma, and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, and it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies. © 2017 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Circulating anti-Mullerian hormone levels in adult men are under a strong genetic influence.

PubMed

Pietiläinen, Kirsi H; Kaprio, Jaakko; Vaaralahti, Kirsi; Rissanen, Aila; Raivio, Taneli

2012-01-01

The determinants of serum anti-Müllerian hormone (AMH) levels in adult men remain unclear. The objective of the study was to investigate the genetic and environmental components in determining postpubertal AMH levels in healthy men. Serum AMH levels, body mass index (BMI), and fat mass (dual energy x-ray absorptiometry) were measured in 64 healthy male (23 monozygotic and 41 dizygotic) twin pairs. Postpubertal AMH levels were highly genetically determined (broad sense heritability 0.92, 95% confidence interval 0.83-0.96). AMH correlated negatively with BMI (r = -0.26, P = 0.030) and fat mass (r = -0.23, P = 0.048). As AMH, BMI had a high heritability (0.68, 95% confidence interval 0.39-0.83), but no genetic correlation was observed between them. AMH levels in men after puberty are under a strong genetic influence. Twin modeling suggests that AMH and BMI are influenced by different sets of genes.

Estimates of genetic and environmental (co)variances for first lactation on milk yield, survival, and calving interval.

PubMed

Dong, M C; van Vleck, L D

1989-03-01

Variance and covariance components for milk yield, survival to second freshening, calving interval in first lactation were estimated by REML with the expectation and maximization algorithm for an animal model which included herd-year-season effects. Cows without calving interval but with milk yield were included. Each of the four data sets of 15 herds included about 3000 Holstein cows. Relationships across herds were ignored to enable inversion of the coefficient matrix of mixed model equations. Quadratics and their expectations were accumulated herd by herd. Heritability of milk yield (.32) agrees with reports by same methods. Heritabilities of survival (.11) and calving interval(.15) are slightly larger and genetic correlations smaller than results from different methods of estimation. Genetic correlation between milk yield and calving interval (.09) indicates genetic ability to produce more milk is lightly associated with decreased fertility.

Genetic conflict between sexual signalling and juvenile survival in the three-spined stickleback.

PubMed

Kim, Sin-Yeon; Velando, Alberto

2016-02-29

Secondary sexual traits and mating preferences may evolve in part because the offspring of attractive males inherit attractiveness and other genetically correlated traits such as fecundity and viability. A problem regarding these indirect genetic mechanisms is how sufficient genetic variation in the traits subject to sexual selection is maintained within a population. Here we explored the additive genetic correlations between carotenoid-based male ornament colouration, female fecundity and juvenile survival rate in the three-spined stickleback (Gasterosteus aculeatus) to test the possibility that attractiveness genes reduce important fitness components in the bearers not expressing the sexual trait. Male sexual attractiveness (i.e., red nuptial colouration) as well as female fecundity and juvenile viability showed heritable variations in the three-spined stickleback. Thus, females can gain indirect benefits by mating with an attractive male. There was a strong positive genetic correlation between female fecundity and juvenile viability. However, red sexual signal of male sticklebacks was negatively genetically correlated with juvenile survival, suggesting genetic conflict between attractiveness and viability. There was no significant correlation between attractiveness of brothers and fecundity of sisters, suggesting no intra-locus sexual conflict. The negative effects of mating with a colourful male on offspring viability may contribute to maintaining the heritable variation under strong directional sexual selection. The strength of indirect sexual selection may be weaker than previously thought due to the hidden genetic conflicts.

The Heritability of Insomnia Progression during Childhood/Adolescence: Results from a Longitudinal Twin Study

PubMed Central

Barclay, Nicola L.; Gehrman, Philip R.; Gregory, Alice M.; Eaves, Lindon J.; Silberg, Judy L.

2015-01-01

Study Objectives: To determine prevalence and heritability of insomnia during middle/late childhood and adolescence; examine longitudinal associations in insomnia over time; and assess the extent to which genetic and environmental factors on insomnia remain stable, or whether new factors come into play, across this developmental period. Design: Longitudinal twin study. Setting: Academic medical center. Patients or Participants: There were 739 complete monozygotic twin pairs (52%) and 672 complete dizygotic twin pairs (48%) initially enrolled and were followed up at three additional time points (waves). Mode ages at each wave were 8, 10, 14, and 15 y (ages ranged from 8–18 y). Interventions: None. Measurements and Results: Clinical ratings of insomnia symptoms were assessed using the Child and Adolescent Psychiatric Assessment (CAPA) by trained clinicians, and rated according to Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition—Revised criteria for presence of “clinically significant insomnia,” over four sequential waves. Insomnia symptoms were prevalent but significantly decreased across the four waves (ranging from 16.6% to 31.2%). “Clinically significant insomnia” was moderately heritable at all waves (h2 range = 14% to 38%), and the remaining source of variance was the nonshared environment. Multivariate models indicated that genetic influences at wave 1 contributed to insomnia at all subsequent waves, and that new genetic influences came into play at wave 2, which further contributed to stability of symptoms. Nonshared environmental influences were time-specific. Conclusion: Insomnia is prevalent in childhood and adolescence, and is moderately heritable. The progression of insomnia across this developmental time period is influenced by stable as well as new genetic factors that come into play at wave 2 (modal age 10 y). Molecular genetic studies should now identify genes related to insomnia progression during childhood and adolescence. Citation: Barclay NL, Gehrman PR, Gregory AM, Eaves LJ, Silberg JL. The heritability of insomnia progression during childhood/adolescence: results from a longitudinal twin study. SLEEP 2015;38(1):109–118. PMID:25325458

Similar recent selection criteria associated with different behavioural effects in two dog breeds.

PubMed

Sundman, A-S; Johnsson, M; Wright, D; Jensen, P

2016-11-01

Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well-defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F 1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F 1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Prevalence and heritability of body dysmorphic symptoms in adolescents and young adults: a population-based nationwide twin study.

PubMed

Enander, Jesper; Ivanov, Volen Z; Mataix-Cols, David; Kuja-Halkola, Ralf; Ljótsson, Brjánn; Lundström, Sebastian; Pérez-Vigil, Ana; Monzani, Benedetta; Lichtenstein, Paul; Rück, Christian

2018-02-28

Body dysmorphic disorder (BDD) usually begins during adolescence but little is known about the prevalence, etiology, and patterns of comorbidity in this age group. We investigated the prevalence of BDD symptoms in adolescents and young adults. We also report on the relative importance of genetic and environmental influences on BDD symptoms, and the risk for co-existing psychopathology. Prevalence of BDD symptoms was determined by a validated cut-off on the Dysmorphic Concerns Questionnaire (DCQ) in three population-based twin cohorts at ages 15 (n = 6968), 18 (n = 3738), and 20-28 (n = 4671). Heritability analysis was performed using univariate model-fitting for the DCQ. The risk for co-existing psychopathology was expressed as odds ratios (OR). The prevalence of clinically significant BDD symptoms was estimated to be between 1 and 2% in the different cohorts, with a significantly higher prevalence in females (1.3-3.3%) than in males (0.2-0.6%). The heritability of body dysmorphic concerns was estimated to be 49% (95% CI 38-54%) at age 15, 39% (95% CI 30-46) at age 18, and 37% (95% CI 29-42) at ages 20-28, with the remaining variance being due to non-shared environment. ORs for co-existing neuropsychiatric and alcohol-related problems ranged from 2.3 to 13.2. Clinically significant BDD symptoms are relatively common in adolescence and young adulthood, particularly in females. The low occurrence of BDD symptoms in adolescent boys may indicate sex differences in age of onset and/or etiological mechanisms. BDD symptoms are moderately heritable in young people and associated with an increased risk for co-existing neuropsychiatric and alcohol-related problems.

The heritability of insomnia progression during childhood/adolescence: results from a longitudinal twin study.

PubMed

Barclay, Nicola L; Gehrman, Philip R; Gregory, Alice M; Eaves, Lindon J; Silberg, Judy L

2015-01-01

To determine prevalence and heritability of insomnia during middle/late childhood and adolescence; examine longitudinal associations in insomnia over time; and assess the extent to which genetic and environmental factors on insomnia remain stable, or whether new factors come into play, across this developmental period. Longitudinal twin study. Academic medical center. There were 739 complete monozygotic twin pairs (52%) and 672 complete dizygotic twin pairs (48%) initially enrolled and were followed up at three additional time points (waves). Mode ages at each wave were 8, 10, 14, and 15 y (ages ranged from 8-18 y). None. Clinical ratings of insomnia symptoms were assessed using the Child and Adolescent Psychiatric Assessment (CAPA) by trained clinicians, and rated according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R criteria for presence of 'clinically significant insomnia', over four sequential waves. Insomnia symptoms were prevalent but significantly decreased across the four waves (ranging from 16.6% to 31.2%). 'Clinically significant insomnia' was moderately heritable at all waves (h² range = 14% to 38%), and the remaining source of variance was the nonshared environment. Multivariate models indicated that genetic influences at wave 1 contributed to insomnia at all subsequent waves, and that new genetic influences came into play at wave 2, which further contributed to stability of symptoms. Nonshared environmental influences were time-specific. Insomnia is prevalent in childhood and adolescence, and is moderately heritable. The progression of insomnia across this developmental time period is influenced by stable as well as new genetic factors that come into play at wave 2 (modal age 10 y). Molecular genetic studies should now identify genes related to insomnia progression during childhood and adolescence. © 2014 Associated Professional Sleep Societies, LLC.

Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke.

PubMed

Adib-Samii, Poneh; Devan, William; Traylor, Matthew; Lanfranconi, Silvia; Zhang, Cathy R; Cloonan, Lisa; Falcone, Guido J; Radmanesh, Farid; Fitzpatrick, Kaitlin; Kanakis, Allison; Rothwell, Peter M; Sudlow, Cathie; Boncoraglio, Giorgio B; Meschia, James F; Levi, Chris; Dichgans, Martin; Bevan, Steve; Rosand, Jonathan; Rost, Natalia S; Markus, Hugh S

2015-02-01

Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses. A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (HSNP=0.23; P=0.0026). HSNP estimates were higher among hypertensive individuals (HSNP=0.45; P=7.99×10(-5)); this increase was greater than expected by chance (P=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (HSNP=0.13; P=0.13). A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wolters Kluwer.

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

PubMed

Darrow, Sabrina M; Hirschtritt, Matthew E; Davis, Lea K; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L; Cath, Danielle C; Greenberg, Erica; Lyon, Gholson J; Yu, Dongmei; McGrath, Lauren M; McMahon, William M; Lee, Paul C; Delucchi, Kevin L; Scharf, Jeremiah M; Mathews, Carol A

2017-04-01

Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated. The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not. The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Genetic Architecture of the Delis-Kaplan Executive Function System Trail Making Test: Evidence for Distinct Genetic Influences on Executive Function

PubMed Central

Vasilopoulos, Terrie; Franz, Carol E.; Panizzon, Matthew S.; Xian, Hong; Grant, Michael D.; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C.; Kremen, William S.

2012-01-01

Objective To examine how genes and environments contribute to relationships among Trail Making test conditions and the extent to which these conditions have unique genetic and environmental influences. Method Participants included 1237 middle-aged male twins from the Vietnam-Era Twin Study of Aging (VESTA). The Delis-Kaplan Executive Function System Trail Making test included visual searching, number and letter sequencing, and set-shifting components. Results Phenotypic correlations among Trails conditions ranged from 0.29 – 0.60, and genes accounted for the majority (58–84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set-shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. Conclusions A common genetic factor, most likely representing a combination of speed and sequencing accounted for most of the correlation among Trails 1–4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set-shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in non-patient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes. PMID:22201299

Genetic parameters for first lactation test-day milk flow in Holstein cows.

PubMed

Laureano, M M M; Bignardi, A B; El Faro, L; Cardoso, V L; Albuquerque, L G

2012-01-01

Genetic parameters for test-day milk flow (TDMF) of 2175 first lactations of Holstein cows were estimated using multiple-trait and repeatability models. The models included the direct additive genetic effect as a random effect and contemporary group (defined as the year and month of test) and age of cow at calving (linear and quadratic effect) as fixed effects. For the repeatability model, in addition to the effects cited, the permanent environmental effect of the animal was also included as a random effect. Variance components were estimated using the restricted maximum likelihood method in single- and multiple-trait and repeatability analyses. The heritability estimates for TDMF ranged from 0.23 (TDMF 6) to 0.32 (TDMF 2 and TDMF 4) in single-trait analysis and from 0.28 (TDMF 7 and TDMF 10) to 0.37 (TDMF 4) in multiple-trait analysis. In general, higher heritabilities were observed at the beginning of lactation until the fourth month. Heritability estimated with the repeatability model was 0.27 and the coefficient of repeatability for first lactation TDMF was 0.66. The genetic correlations were positive and ranged from 0.72 (TDMF 1 and 10) to 0.97 (TDMF 4 and 5). The results indicate that milk flow should respond satisfactorily to selection, promoting rapid genetic gains because the estimated heritabilities were moderate to high. Higher genetic gains might be obtained if selection was performed in the TDMF 4. Both the repeatability model and the multiple-trait model are adequate for the genetic evaluation of animals in terms of milk flow, but the latter provides more accurate estimates of breeding values.

Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS:SFHS).

PubMed

Fernandez-Pujals, Ana Maria; Adams, Mark James; Thomson, Pippa; McKechanie, Andrew G; Blackwood, Douglas H R; Smith, Blair H; Dominiczak, Anna F; Morris, Andrew D; Matthews, Keith; Campbell, Archie; Linksted, Pamela; Haley, Chris S; Deary, Ian J; Porteous, David J; MacIntyre, Donald J; McIntosh, Andrew M

2015-01-01

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

PubMed

Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra; Cox, Nancy J; Van Cauter, Eve; Davis, Lea K

2018-01-01

Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate. © 2017 by the American Diabetes Association.

Heritability of Respiratory Infection with Pseudomonas aeruginosa in Cystic Fibrosis

PubMed Central

Green, Deanna M.; Collaco, J. Michael; McDougal, Kathryn E.; Naughton, Kathleen M.; Blackman, Scott M.; Cutting, Garry R.

2013-01-01

Objective To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Study design Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Results Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, −0.352 to 0.607), generating a heritability of 0.85. Conclusion Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis. PMID:22364820

Marker-based quantitative genetics in the wild?: the heritability and genetic correlation of chemical defenses in eucalyptus.

PubMed

Andrew, R L; Peakall, R; Wallis, I R; Wood, J T; Knight, E J; Foley, W J

2005-12-01

Marker-based methods for estimating heritability and genetic correlation in the wild have attracted interest because traditional methods may be impractical or introduce bias via G x E effects, mating system variation, and sampling effects. However, they have not been widely used, especially in plants. A regression-based approach, which uses a continuous measure of genetic relatedness, promises to be particularly appropriate for use in plants with mixed-mating systems and overlapping generations. Using this method, we found significant narrow-sense heritability of foliar defense chemicals in a natural population of Eucalyptus melliodora. We also demonstrated a genetic basis for the phenotypic correlation underlying an ecological example of conditioned flavor aversion involving different biosynthetic pathways. Our results revealed that heritability estimates depend on the spatial scale of the analysis in a way that offers insight into the distribution of genetic and environmental variance. This study is the first to successfully use a marker-based method to measure quantitative genetic parameters in a tree. We suggest that this method will prove to be a useful tool in other studies and offer some recommendations for future applications of the method.

Prevalence and heritability of psoriasis and benign migratory glossitis in one Brazilian population.

PubMed

Jorge, Maria Augusta; Gonzaga, Heron Fernando de Sousa; Tomimori, Jane; Picciani, Bruna Lavinas Sayed; Barbosa, Calógeras Antônio

2017-01-01

An oral condition associated to psoriasis is benign migratory glossitis. The review of the literature does not show any publication about heritability in both soriasis and benign migratory glossitis and prevalence of psoriasis in the Brazilian population. This research was carried out in order to determine the prevalence of psoriasis and benign migratory glossitis in the Brazilian population from a Brazilian sample, as well as the heritability in these conditions. Six thousand patients were studied from the records of the outpatient dermatology department. The sample had 129 patients with cutaneous psoriasis, 399 with benign migratory glossitis without psoriasis and a control group with 5,472 patients. After data collection, the statistical analysis was made using Woolf, Chi-square and Falconer tests. The prevalence of psoriasis was 2.15% and the benign migratory glossitis was 7.0%. The prevalence of benign migratory glossitis in the psoriasis group was high (16.3%), and that was statistically significant. Family history in the psoriasis group was 38% for the condition itself and 2,75% for benign migratory glossitis and in the benign migratory glossitis group was 17.54% for the condition itself and 1.5% for psoriasis. The study of heritability was 38.8% for psoriasis and 36.6% for benign migratory glossitis, both with medium heritability. This study was only in the state of São Paulo. This is the first publication that quantifies how much of these conditions have a genetic background and how important the environmental factors are in triggering them.

Quantifying the uncertainty in heritability.

PubMed

Furlotte, Nicholas A; Heckerman, David; Lippert, Christoph

2014-05-01

The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach, in which heritability is estimated using maximum likelihood and its variance is quantified through an asymptotic normal approximation. An alternative approach is to quantify the uncertainty in heritability through its Bayesian posterior distribution. In this paper, we develop the latter approach, make it computationally efficient and compare it to the frequentist approach. We show theoretically that, for a sufficiently large sample size and intermediate values of heritability, the two approaches provide similar results. Using the Atherosclerosis Risk in Communities cohort, we show empirically that the two approaches can give different results and that the variance/uncertainty can remain large.

75 FR 68802 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

... Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting In accordance with... following meeting: Name: Secretary's Advisory Committee on Heritable Disorders in Newborns and Children... Committee on Heritable Disorders in Newborns and Children (Advisory Committee) was established to advise and...

The heritability of vessel size of the pampiniform plexus as a means to assess the genetic component of varicocele

USDA-ARS?s Scientific Manuscript database

Ultrasonography of each testicle was used to capture a coronal-saggital image of the veins of the pampiniform plexus (PP) and the testicular artery of 239 boars at approximately 6 months of age. Three to 10 vessels of the PP were used to derive the average area of right PP vessels (AAR) and the aver...

Evidence for heritability of adult men's sexual interest in youth under age 16 from a population-based extended twin design.

PubMed

Alanko, Katarina; Salo, Benny; Mokros, Andreas; Santtila, Pekka

2013-04-01

Sexual interest in children resembles sexual gender orientation in terms of early onset and stability across the life span. Although a genetic component to sexual interest in children seems possible, no research has addressed this question to date. Prior research showing familial transmission of pedophilia remains inconclusive about shared environmental or genetic factors. Studies from the domains of sexual orientation and sexually problematic behavior among children pointed toward genetic components. Adult men's sexual interest in youthfulness-related cues may be genetically influenced. The aim of the present study was to test whether male sexual interest in children and youth under age 16 involves a heritable component. The main outcome measure was responses in a confidential survey concerning sexual interest, fantasies, or activity pertaining to children under the age of 16 years during the previous 12 months. The present study used an extended family design within behavioral genetic modeling to estimate the contributions of genetic and environmental factors in the occurrence of adult men's sexual interest in children and youth under age 16. Participants were male twins and their male siblings from a population-based Finnish cohort sample aged 21-43 years (N = 3,967). The incidence of sexual interest in children under age was 3%. Twin correlations were higher for monozygotic than for dizygotic twins. Behavioral genetic model fitting indicated that a model including genetic effects as well as nonshared environmental influences (including measurement error), but not common environmental influences, fits the data best. The amount of variance attributable to nonadditive genetic influences (heritability) was estimated at 14.6%. The present study provides the first indication that genetic influences may play a role in shaping sexual interest toward children and adolescents among adult men. Compared with the variance attributable to nonshared environmental effects (plus measurement error), the contribution of any genetic factors seems comparatively weak. Future research should address the possible interplay of genetic with environmental risk factors, such as own sexual victimization in childhood. © 2013 International Society for Sexual Medicine.

Genetic Analysis of Growth Traits in Polled Nellore Cattle Raised on Pasture in Tropical Region Using Bayesian Approaches

PubMed Central

Lopes, Fernando Brito; Magnabosco, Cláudio Ulhôa; Paulini, Fernanda; da Silva, Marcelo Corrêa; Miyagi, Eliane Sayuri; Lôbo, Raysildo Barbosa

2013-01-01

Components of (co)variance and genetic parameters were estimated for adjusted weights at ages 120 (W120), 240 (W240), 365 (W365) and 450 (W450) days of Polled Nellore cattle raised on pasture and born between 1987 and 2010. Analyses were performed using an animal model, considering fixed effects: herd-year-season of birth and calf sex as contemporary groups and the age of cow as a covariate. Gibbs Samplers were used to estimate (co)variance components, genetic parameters and additive genetic effects, which accounted for great proportion of total variation in these traits. High direct heritability estimates for the growth traits were revealed and presented mean 0.43, 0.61, 0.72 and 0.67 for W120, W240, W365 and W450, respectively. Maternal heritabilities were 0.07 and 0.08 for W120 and W240, respectively. Direct additive genetic correlations between the weight at 120, 240, 365 and 450 days old were strong and positive. These estimates ranged from 0.68 to 0.98. Direct-maternal genetic correlations were negative for W120 and W240. The estimates ranged from −0.31 to −0.54. Estimates of maternal heritability ranged from 0.056 to 0.092 for W120 and from 0.064 to 0.096 for W240. This study showed that genetic progress is possible for the growth traits we studied, which is a novel and favorable indicator for an upcoming and promising Polled Zebu breed in Tropical regions. Maternal effects influenced the performance of weight at 120 and 240 days old. These effects should be taken into account in genetic analyses of growth traits by fitting them as a genetic or a permanent environmental effect, or even both. In general, due to a medium-high estimate of environmental (co)variance components, management and feeding conditions for Polled Nellore raised at pasture in tropical regions of Brazil needs improvement and growth performance can be enhanced. PMID:24040412

Serum antibody responses in pigs trickle-infected with Ascaris and Trichuris: Heritabilities and associations with parasitological findings.

PubMed

Kringel, Helene; Thamsborg, Stig Milan; Petersen, Heidi Huus; Göring, Harald Heinz Herbert; Skallerup, Per; Nejsum, Peter

2015-07-30

A humoral immune response following helminth infection in pigs is well documented. However, it has been difficult to confirm the existence of antibody mediated resistance against the large roundworm, Ascaris suum, and whipworm, Trichuris suis, in experimental settings by correlating worm burdens or egg excretion with specific antibody levels. We set out to investigate the association between worm load and T. suis and A. suum specific serum antibody levels (IgG1, IgG2 and IgA) against excretory-secretory products of adults and third stage larvae, respectively, measured at 0, 7 and 14 weeks p.i. in a trickle-infected F1-resource-population of crossbred pigs (n=195). Furthermore, we wanted to determine the heritability of these antibody isotypes during the course of infection. Most pigs remained infected with A. suum throughout the experiment while they expelled T. suis between 7 and 14 weeks post infection (p.i.). Parasite specific IgG1 and IgA were significantly (P<0.001) elevated after 7 and 14 weeks of infection, whereas parasite specific IgG2 levels only changed slightly at 14 weeks p.i.. However, the observed association between specific antibody isotype levels and faecal egg counts and macroscopic worm load was weak. The relative heritabilities of the different parasite specific isotypes were assessed and resulted in significant heritability estimates for parasite specific IgG1 and IgA. The highest heritabilities were found for A. suum specific IgG1 (h(2)=0.41 and 0.46 at 7 and 14 weeks p.i., respectively). Thus, the present study demonstrates that host genetic factors influence the IgG1 and IgA antibody isotype responses specific to two of the most common gastrointestinal nematodes of swine whereas specific antibody levels were poorly associated with egg excretion and the presence of macroscopic worms. Copyright © 2015. Published by Elsevier B.V.

Novel Molecular Therapies for Heritable Skin Disorders

PubMed Central

Uitto, Jouni; Christiano, Angela M.; Irwin McLean, W. H.; McGrath, John A.

2013-01-01

Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena. PMID:22158553

A novel measure of ewe efficiency for breeding and benchmarking purposes.

PubMed

McHugh, Nóirín; Pabiou, Thierry; McDermott, Kevin; Wall, Eamon; Berry, Donagh P

2018-06-04

Ewe efficiency has traditionally been defined as the ratio of litter weight to ewe weight; given the statistical properties of ratio traits, an alternative strategy is proposed in the present study. The concept of using the deviation in performance of an animal from the population norm has grown in popularity as a measure of animal-level efficiency. The objective of the present study was to define novel measures of efficiency for sheep, which considers the combined weight of a litter of lambs relative to the weight of their dam, and vice versa. Two novel traits, representing the deviation in total litter weight at 40 d (DEV40L) or weaning (DEVweanL), were calculated as the residuals of a statistical model, with litter weight as the dependent variable and with the fixed effects of litter rearing size, contemporary group, and ewe weight. The deviation in ewe weight at 40-d postlambing (DEV40E) or weaning (DEVweanE) was derived using a similar approach but with ewe weight and litter weight interchanged as the dependent variable. Variance components for each trait were estimated by first deriving the litter or ewe weight deviation phenotype and subsequently estimating the variance components. The phenotypic SD in DEV40L and DEVweanL was 8.46 and 15.37 kg, respectively; the mean litter weight at 40 d and weaning was 30.97 and 47.68 kg, respectively. The genetic SD and heritability for DEV40L was 2.65 kg and 0.12, respectively. For DEVweanL, the genetic SD and heritability was 4.94 kg and 0.13, respectively. The average ewe weight at 40-d postlambing and at weaning was 66.43 and 66.87 kg, respectively. The genetic SD and heritability for DEV40E was 4.33 kg and 0.24, respectively. The heritability estimated for DEVweanE was 0.31. The traits derived in the present study may be useful not only for phenotypic benchmarking of ewes within flock on performance but also for benchmarking flocks against each other; furthermore, the extent of genetic variability in all traits, coupled with the fact that the data required to generate these novel phenotypes are usually readily available, signals huge potential within sheep breeding programs.

Quantifying the uncertainty in heritability

PubMed Central

Furlotte, Nicholas A; Heckerman, David; Lippert, Christoph

2014-01-01

The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach, in which heritability is estimated using maximum likelihood and its variance is quantified through an asymptotic normal approximation. An alternative approach is to quantify the uncertainty in heritability through its Bayesian posterior distribution. In this paper, we develop the latter approach, make it computationally efficient and compare it to the frequentist approach. We show theoretically that, for a sufficiently large sample size and intermediate values of heritability, the two approaches provide similar results. Using the Atherosclerosis Risk in Communities cohort, we show empirically that the two approaches can give different results and that the variance/uncertainty can remain large. PMID:24670270

Genetic analysis of clinical findings at health examinations of young Swedish warmblood riding horses

PubMed Central

2013-01-01

Background Soundness is important for welfare and utility of the riding horse. Musculoskeletal disorders are the most common causes of interruption in training and of culling. Despite great importance, heritability of a majority of health traits in horses has previously not been estimated. The objective was to perform genetic analyses of medical and orthopaedic health traits in young riding horses, including estimates of heritability and genetic correlations between health traits, and to reveal possibilities for genetic evaluation of stallions for progeny health. Results The heritability of health traits was estimated using records from 8,238 Swedish warmblood riding horses examined as 4–5 year olds at the Riding Horse Quality Test in 1983–2005. The analyses were performed using multi-trait linear mixed animal models. The heritabilities of palpatory orthopaedic health (PALP), including effusion, swelling, heat, soreness and stiffness/atrophy, and hoof examination results (HOOF), of hoof shape and hoof wall quality, were 0.12 and 0.10, respectively. The genetic variation in these traits resulted in distinct health differences between progeny groups of stallions. The highest heritability among clinical signs of PALP was found for synovial effusions at 0.14. For systemic locations, joint related findings had the highest heritability; 0.13. The heritabilities of medical health and locomotion examination results were low, 0.02 and 0.04, respectively. A genetic improvement of health status has occurred over time but accounts only partly for the decrease in clinical findings of health during the studied period. Conclusions The genetic variation found in PALP and HOOF implies distinct differences between progeny groups. Thus, there are possibilities for improvement of these traits in the population through selection. The weak and non-significant correlation between PALP and HOOF suggests that both traits need to be selected for in practical breeding to improve both traits. Some genetic improvements over time have already been achieved, possibly due to regular stallion health inspections and an indirect selection for lifetime performance. For further improvements stallion breeding values for health may be introduced, based on RHQT examinations, complementary to present breeding values for performance. PMID:23510509

Lack of evidence for allelic association between personality traits and the dopamine D4 receptor gene polymorphisms.

PubMed

Jönsson, E G; Nöthen, M M; Gustavsson, J P; Neidt, H; Brené, S; Tylec, A; Propping, P; Sedvall, G C

1997-05-01

Personality traits in human subjects have shown considerable heritable components. Recently, two research groups reported associations between dopamine D4 receptor genotypes and the personality trait known as novelty seeking. This study was an attempt to replicate these findings. Three different exonic dopamine D4 receptor polymorphisms were genotyped in 126 healthy Swedish subjects. Personality traits of the subjects were assessed with the Karolinska Scales of Personality. Although there was a tendency in the direction hypothesized, no significant association between genotype constellations and personality traits was found. The previously reported association between dopamine D4 receptor alleles and novelty seeking was not replicated. Possible reasons for this include differences in personality inventories, ethnicity, and type I or type II errors.

Quantifying the heritability of testicular germ cell tumour using both population-based and genomic approaches.

PubMed

Litchfield, Kevin; Thomsen, Hauke; Mitchell, Jonathan S; Sundquist, Jan; Houlston, Richard S; Hemminki, Kari; Turnbull, Clare

2015-09-09

A sizable fraction of testicular germ cell tumour (TGCT) risk is expected to be explained by heritable factors. Recent genome-wide association studies (GWAS) have successfully identified a number of common SNPs associated with TGCT. It is however, unclear how much common variation there is left to be accounted for by other, yet to be identified, common SNPs and what contribution common genetic variation makes to the heritable risk of TGCT. We approached this question using two complimentary analytical techniques. We undertook a population-based analysis of the Swedish family-cancer database, through which we estimated that the heritability of TGCT at 48.9% (CI:47.2%-52.3%). We also applied Genome-Wide Complex Trait Analysis to 922 cases and 4,842 controls to estimate the heritability of TGCT. The heritability explained by known common risk SNPs identified by GWAS was 9.1%, whereas the heritability explained by all common SNPs was 37.4% (CI:27.6%-47.2%). These complementary findings indicate that the known TGCT SNPs only explain a small proportion of the heritability and many additional common SNPs remain to be identified. The data also suggests that a fraction of the heritability of TGCT is likely to be explained by other classes of genetic variation, such as rare disease-causing alleles.

Genetic variability and heritability of chlorophyll a fluorescence parameters in Scots pine (Pinus sylvestris L.).

PubMed

Čepl, Jaroslav; Holá, Dana; Stejskal, Jan; Korecký, Jiří; Kočová, Marie; Lhotáková, Zuzana; Tomášková, Ivana; Palovská, Markéta; Rothová, Olga; Whetten, Ross W; Kaňák, Jan; Albrechtová, Jana; Lstibůrek, Milan

2016-07-01

Current knowledge of the genetic mechanisms underlying the inheritance of photosynthetic activity in forest trees is generally limited, yet it is essential both for various practical forestry purposes and for better understanding of broader evolutionary mechanisms. In this study, we investigated genetic variation underlying selected chlorophyll a fluorescence (ChlF) parameters in structured populations of Scots pine (Pinus sylvestris L.) grown on two sites under non-stress conditions. These parameters were derived from the OJIP part of the ChlF kinetics curve and characterize individual parts of primary photosynthetic processes associated, for example, with the exciton trapping by light-harvesting antennae, energy utilization in photosystem II (PSII) reaction centers (RCs) and its transfer further down the photosynthetic electron-transport chain. An additive relationship matrix was estimated based on pedigree reconstruction, utilizing a set of highly polymorphic single sequence repeat markers. Variance decomposition was conducted using the animal genetic evaluation mixed-linear model. The majority of ChlF parameters in the analyzed pine populations showed significant additive genetic variation. Statistically significant heritability estimates were obtained for most ChlF indices, with the exception of DI0/RC, φD0 and φP0 (Fv/Fm) parameters. Estimated heritabilities varied around the value of 0.15 with the maximal value of 0.23 in the ET0/RC parameter, which indicates electron-transport flux from QA to QB per PSII RC. No significant correlation was found between these indices and selected growth traits. Moreover, no genotype × environment interaction (G × E) was detected, i.e., no differences in genotypes' performance between sites. The absence of significant G × E in our study is interesting, given the relatively low heritability found for the majority of parameters analyzed. Therefore, we infer that polygenic variability of these indices is selectively neutral. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Familial influence and childhood trauma in female alcoholism

PubMed Central

Magnusson, Å.; Lundholm, C.; Göransson, M.; Copeland, W.; Heilig, M.; Pedersen, N. L.

2013-01-01

Background To assess the role of genetic and environmental factors in female alcoholism using a large population-based twin sample, taking into account possible differences between early and late onset disease subtype. Method Twins aged 20–47 years from the Swedish Twin Registry (n = 24 119) answered questions to establish lifetime alcohol use disorders. Subjects with alcoholism were classified for subtype. Structural equation modeling was used to quantify the proportion of phenotypic variance due to genetic and environmental factors and test whether heritability in women differed from that in men. The association between childhood trauma and alcoholism was then examined in females, controlling for background familial factors. Results Lifetime prevalence of alcohol dependence was 4.9% in women and 8.6% in men. Overall, heritability for alcohol dependence was 55%, and did not differ significantly between men and women, although women had a significantly greater heritability for late onset (type I). Childhood physical trauma and sexual abuse had a stronger association with early onset compared to late onset alcoholism [odds ratio (OR) 2.54, 95% confidence interval (CI) 1.53–3.88 and OR 2.29, 95% CI 1.38–3.79 respectively]. Co-twin analysis indicated that familial factors largely accounted for the influence of physical trauma whereas the association with childhood sexual abuse reflected both familial and specific effects. Conclusions Heritability of alcoholism in women is similar to that in men. Early onset alcoholism is strongly association with childhood trauma, which seems to be both a marker of familial background factors and a specific individual risk factor per se. PMID:21798111

Relevance of genetic relationship in GWAS and genomic prediction.

PubMed

Pereira, Helcio Duarte; Soriano Viana, José Marcelo; Andrade, Andréa Carla Bastos; Fonseca E Silva, Fabyano; Paes, Geísa Pinheiro

2018-02-01

The objective of this study was to analyze the relevance of relationship information on the identification of low heritability quantitative trait loci (QTLs) from a genome-wide association study (GWAS) and on the genomic prediction of complex traits in human, animal and cross-pollinating populations. The simulation-based data sets included 50 samples of 1000 individuals of seven populations derived from a common population with linkage disequilibrium. The populations had non-inbred and inbred progeny structure (50 to 200) with varying number of members (5 to 20). The individuals were genotyped for 10,000 single nucleotide polymorphisms (SNPs) and phenotyped for a quantitative trait controlled by 10 QTLs and 90 minor genes showing dominance. The SNP density was 0.1 cM and the narrow sense heritability was 25%. The QTL heritabilities ranged from 1.1 to 2.9%. We applied mixed model approaches for both GWAS and genomic prediction using pedigree-based and genomic relationship matrices. For GWAS, the observed false discovery rate was kept below the significance level of 5%, the power of detection for the low heritability QTLs ranged from 14 to 50%, and the average bias between significant SNPs and a QTL ranged from less than 0.01 to 0.23 cM. The QTL detection power was consistently higher using genomic relationship matrix. Regardless of population and training set size, genomic prediction provided higher prediction accuracy of complex trait when compared to pedigree-based prediction. The accuracy of genomic prediction when there is relatedness between individuals in the training set and the reference population is much higher than the value for unrelated individuals.

Complex Variation in Measures of General Intelligence and Cognitive Change

PubMed Central

Rowe, Suzanne J.; Rowlatt, Amy; Davies, Gail; Harris, Sarah E.; Porteous, David J.; Liewald, David C.; McNeill, Geraldine; Starr, John M.

2013-01-01

Combining information from multiple SNPs may capture a greater amount of genetic variation than from the sum of individual SNP effects and help identifying missing heritability. Regions may capture variation from multiple common variants of small effect, multiple rare variants or a combination of both. We describe regional heritability mapping of human cognition. Measures of crystallised (gc) and fluid intelligence (gf) in late adulthood (64–79 years) were available for 1806 individuals genotyped for 549,692 autosomal single nucleotide polymorphisms (SNPs). The same individuals were tested at age 11, enabling us the rare opportunity to measure cognitive change across most of their lifespan. 547,750 SNPs ranked by position are divided into 10, 908 overlapping regions of 101 SNPs to estimate the genetic variance each region explains, an approach that resembles classical linkage methods. We also estimate the genetic variation explained by individual autosomes and by SNPs within genes. Empirical significance thresholds are estimated separately for each trait from whole genome scans of 500 permutated data sets. The 5% significance threshold for the likelihood ratio test of a single region ranged from 17–17.5 for the three traits. This is the equivalent to nominal significance under the expectation of a chi-squared distribution (between 1df and 0) of P<1.44×10−5. These thresholds indicate that the distribution of the likelihood ratio test from this type of variance component analysis should be estimated empirically. Furthermore, we show that estimates of variation explained by these regions can be grossly overestimated. After applying permutation thresholds, a region for gf on chromosome 5 spanning the PRRC1 gene is significant at a genome-wide 10% empirical threshold. Analysis of gene methylation on the temporal cortex provides support for the association of PRRC1 and fluid intelligence (P = 0.004), and provides a prime candidate gene for high throughput sequencing of these uniquely informative cohorts. PMID:24349040

Heritable and non-heritable pathways to early callous-unemotional behaviors

PubMed Central

Hyde, Luke W.; Waller, Rebecca; Trentacosta, Christopher J.; Shaw, Daniel S.; Neiderhiser, Jenae M.; Ganiban, Jody M.; Reiss, David; Leve, Leslie D.

2016-01-01

Objective Callous-unemotional behaviors in early childhood identify children at high risk for severe trajectories of antisocial behavior and callous-unemotional traits that culminate in later diagnoses of conduct disorder, antisocial personality disorder, and psychopathy. Studies have demonstrated high heritability of callous-unemotional traits, but little research has examined specific heritable pathways to earlier callous-unemotional behaviors. Additionally, studies indicate that positive parenting protects against the development of callous-unemotional traits, but genetically informed designs have not been used to confirm that these relationships are not the product of gene-environment correlations. Method Using an adoption cohort of 561 families, biological mothers reported their history of severe antisocial behavior. Observations of adoptive mother positive reinforcement at 18 months were examined as predictors of callous-unemotional behaviors when children were 27 months old. Results Biological mother antisocial behavior predicted early callous-unemotional behaviors despite having no or limited contact with offspring. Adoptive mother positive reinforcement protected against early callous-unemotional behaviors in children not genetically related to the parent. High levels of adoptive mother positive reinforcement buffered the effects of heritable risk for callous-unemotional behaviors posed by biological mother antisocial behavior. Conclusions The findings elucidate heritable and non-heritable pathways to early callous-unemotional behaviors. The results provide a specific heritable pathway to callous-unemotional behaviors and compelling evidence that parenting is an important non-heritable factor in the development of callous-unemotional behaviors. As positive reinforcement buffered heritable risk for callous-unemotional behaviors, these findings have important translational implications for the prevention of trajectories to serious antisocial behavior. PMID:27056607

Endocrine Disruptors and the Breast: Early Life Effects and Later Life Disease

PubMed Central

Macon, Madisa B.

2013-01-01

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5–27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future. PMID:23417729

Endocrine disruptors and the breast: early life effects and later life disease.

PubMed

Macon, Madisa B; Fenton, Suzanne E

2013-03-01

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5-27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future.

Does the heritability of cognitive abilities vary as a function of parental education? Evidence from a German twin sample.

PubMed

Spengler, Marion; Gottschling, Juliana; Hahn, Elisabeth; Tucker-Drob, Elliot M; Harzer, Claudia; Spinath, Frank M

2018-01-01

A well-known hypothesis in the behavioral genetic literature predicts that the heritability of cognitive abilities is higher in the presence of higher socioeconomic contexts. However, studies suggest that the effect of socioeconomic status (SES) on the heritability of cognitive ability may not be universal, as it has mostly been demonstrated in the United States, but not in other Western nations. In the present study we tested whether the importance of genetic and environmental effects on cognitive abilities varies as a function of parental education in a German twin sample. Cognitive ability scores (general, verbal, and nonverbal) were obtained on 531 German twin pairs (192 monozygotic, 339 dizygotic, ranging from 7 to 14 years of age; Mage = 10.25, SD = 1.83). Data on parental education were available from mothers and fathers. Results for general cognitive ability and nonverbal ability indicated no significant gene x parental education interaction effect. For verbal ability, a significant nonshared environment (E) x parental education interaction was found in the direction of greater nonshared environmental influences on verbal abilities among children raised by more educated parents.

Etiology of Stability and Growth of Internalizing and Externalizing Behavior Problems Across Childhood and Adolescence.

PubMed

Hatoum, Alexander S; Rhee, Soo Hyun; Corley, Robin P; Hewitt, John K; Friedman, Naomi P

2018-04-20

Internalizing and externalizing behaviors are heritable, and show genetic stability during childhood and adolescence. Less work has explored how genes influence individual differences in developmental trajectories. We estimated ACE biometrical latent growth curve models for the Teacher Report Form (TRF) and parent Child Behavior Checklist (CBCL) internalizing and externalizing scales from ages 7 to 16 years in 408 twin pairs from the Colorado Longitudinal Twin Study. We found that Intercept factors were highly heritable for both internalizing and externalizing behaviors (a2 = .61-.92), with small and nonsignificant environmental influences for teacher-rated data but significant nonshared environmental influences for parent-rated data. There was some evidence of heritability of decline in internalizing behavior (Slopes for teacher and parent ratings), but the Slope genetic variance was almost entirely shared with that for the Intercept when different than zero. These results suggest that genetic effects on these developmental trajectories operate primarily on initial levels and stability, with no significant unique genetic influences for change. Finally, cross-rater analyses of the growth factor scores revealed moderate to large genetic and environmental associations between growth factors derived from parents' and teachers' ratings, particularly the Intercepts.

Identification of quantitative trait loci for fibrin clot phenotypes: The EuroCLOT study

PubMed Central

Williams, Frances MK; Carter, Angela M; Kato, Bernet; Falchi, Mario; Bathum, Lise; Surdulescu, Gabriela; Kyvik, Kirsten Ohm; Palotie, Aarno; Spector, Tim D; Grant, Peter J

2012-01-01

Objectives Fibrin makes up the structural basis of an occlusive arterial thrombus and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to 1) determine the heritability of fibrin phenotypes and 2) identify QTLs associated with fibrin phenotypes. Methods 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK Caucasian female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Results Estimates of heritability for d-dimer and turbidometric variables were in the range 17 - 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD>3 on 5 chromosomes (5, 6, 9, 16 and 17). Conclusions The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischaemic cardiovascular disorders and their therapy. PMID:19150881

Genetics of regular exercise and sedentary behaviors.

PubMed

de Geus, Eco J C; Bartels, Meike; Kaprio, Jaakko; Lightfoot, J Timothy; Thomis, Martine

2014-08-01

Studies on the determinants of physical activity have traditionally focused on social factors and environmental barriers, but recent research has shown the additional importance of biological factors, including genetic variation. Here we review the major tenets of this research to arrive at three major conclusions: First, individual differences in physical activity traits are significantly influenced by genetic factors, but genetic contribution varies strongly over age, with heritability of leisure time exercise behavior ranging from 27% to 84% and heritability of sedentary behaviors ranging from 9% to 48%. Second, candidate gene approaches based on animal or human QTLs or on biological relevance (e.g., dopaminergic or cannabinoid activity in the brain, or exercise performance influencing muscle physiology) have not yet yielded the necessary evidence to specify the genetic mechanisms underlying the heritability of physical activity traits. Third, there is significant genetic modulation of the beneficial effects of daily physical activity patterns on strength and endurance improvements and on health-related parameters like body mass index. Further increases in our understanding of the genetic determinants of sedentary and exercise behaviors as well as the genetic modulation of their effects on fitness and health will be key to meaningful future intervention on these behaviors.

Use of support vector machines for disease risk prediction in genome-wide association studies: concerns and opportunities.

PubMed

Mittag, Florian; Büchel, Finja; Saad, Mohamad; Jahn, Andreas; Schulte, Claudia; Bochdanovits, Zoltan; Simón-Sánchez, Javier; Nalls, Mike A; Keller, Margaux; Hernandez, Dena G; Gibbs, J Raphael; Lesage, Suzanne; Brice, Alexis; Heutink, Peter; Martinez, Maria; Wood, Nicholas W; Hardy, John; Singleton, Andrew B; Zell, Andreas; Gasser, Thomas; Sharma, Manu

2012-12-01

The success of genome-wide association studies (GWAS) in deciphering the genetic architecture of complex diseases has fueled the expectations whether the individual risk can also be quantified based on the genetic architecture. So far, disease risk prediction based on top-validated single-nucleotide polymorphisms (SNPs) showed little predictive value. Here, we applied a support vector machine (SVM) to Parkinson disease (PD) and type 1 diabetes (T1D), to show that apart from magnitude of effect size of risk variants, heritability of the disease also plays an important role in disease risk prediction. Furthermore, we performed a simulation study to show the role of uncommon (frequency 1-5%) as well as rare variants (frequency <1%) in disease etiology of complex diseases. Using a cross-validation model, we were able to achieve predictions with an area under the receiver operating characteristic curve (AUC) of ~0.88 for T1D, highlighting the strong heritable component (∼90%). This is in contrast to PD, where we were unable to achieve a satisfactory prediction (AUC ~0.56; heritability ~38%). Our simulations showed that simultaneous inclusion of uncommon and rare variants in GWAS would eventually lead to feasible disease risk prediction for complex diseases such as PD. The used software is available at http://www.ra.cs.uni-tuebingen.de/software/MACLEAPS/. © 2012 Wiley Periodicals, Inc.

Evolutionary ecology of telomeres: a review.

PubMed

Olsson, Mats; Wapstra, Erik; Friesen, Christopher R

2018-06-01

Telomere-induced selection could take place if telomere-associated disease risk shortens reproductive life span and differently reduces relative fitness among individuals. Some of these diseases first appear before reproductive senescence and could thus influence ongoing selection. We ask whether we can estimate the components of the breeder's equation for telomeres, in which the response to selection (R, by definition "evolution") is the product of ongoing selection (S) and heritability (h 2 ). However, telomere inheritance is a conundrum: in quantitative genetics, traits can usually be allocated to categories with relatively high or low heritability, depending on their association with relative fitness. Telomere traits, however, show wide variation in heritability from zero to one, across taxa, gender, ethnicity, age, and disease status. In spite of this, there is divergence in telomere length among populations, supporting past and ongoing telomere evolution. Rates of telomere attrition and elongation vary among taxa with some, but not complete, taxonomic coherence. For example, telomerase is commonly referred to as "restricted to the germ line in mammals," but inbred mice and beavers have telomerase upregulation in somatic tissue, as do many ectotherms. These observations provoke a simplistic understanding of telomere evolutionary biology-clearly much is yet to be discovered. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of The New York Academy of Sciences.

Inferring genetic parameters on latent variables underlying milk yield and quality, protein composition, curd firmness and cheese-making traits in dairy cattle.

PubMed

Dadousis, C; Cipolat-Gotet, C; Bittante, G; Cecchinato, A

2018-02-01

We studied the genetics of cheese-related latent variables (factors; Fs) for application in dairy cattle breeding. In total, 26 traits, recorded in 1264 Brown Swiss cows, were analyzed through multivariate factor analysis (MFA). Traits analyzed were descriptors of milk quality and yield (including protein fractions) and measures of coagulation, curd firmness (CF), cheese yields (%CY) and nutrient recoveries in the curd (REC). A total of 10 Fs (mutual orthogonal with a varimax rotation) were obtained. To assess the practical use of the Fs into breeding, we inferred their genetic parameters using single and bivariate animal models under a Bayesian framework. Heritability estimates (intra-herd) varied between 0.11 and 0.72 (F3: Yield and F7: κ-β-CN, respectively). The Fs underlined basic characteristics of the cheese-making process, milk components and udder health, while retaining 74% of the original variability. The first two Fs were indicators of the CY percentage (F1: %CY) and the CF process (F2: CF t ), and presented similar heritability estimates: 0.268 and 0.295, respectively. The third factor was associated with the yield of milk and solids (F3: Yield) characterized by a low heritability (0.108) and the fourth with the cheese nitrogen (N) (F4: Cheese N) that conversely appeared to be characterized by a high heritability (0.618). Three Fs were associated with the proportion of the basic milk caseins on total milk protein (F5: as1-β-CN, F7: κ-β-CN, F8: as2-CN), also highly heritable (0.565, 0.723 and 0.397, respectively) and 1 factor with the phosphorylated form of the as1-CN (F9: as1-CN-Ph; 0.318). Moreover, 1 factor was linked to the whey protein α-LA (F10: α-LA; 0.147). An indicator factor of a cow's udder health (F6: Udder health) was also obtained and showed a moderate heritability (0.204). Although the Fs were phenotypically uncorrelated, considerable additive genetic correlations existed among them, with highest values observed between F10: α-LA and F6: Udder health (-0.67) as well as between F9: as1-CN-Ph and F3: Yield (-0.60). Our results show the usefulness of MFA in dairy cattle breeding. The ability to replace a large number of variables with a few latent indicators of the same biological meaning marks MFA as a valuable tool for developing breeding strategies to improve cow's cheese-related traits.

No Genetic Influence for Childhood Behavior Problems From DNA Analysis

PubMed Central

Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

2013-01-01

Objective Twin studies of behavior problems in childhood point to substantial genetic influence. It is now possible to estimate genetic influence using DNA alone in samples of unrelated individuals, not relying on family-based designs such as twins. A linear mixed model, which incorporates DNA microarray data, has confirmed twin results by showing substantial genetic influence for diverse traits in adults. Here we present direct comparisons between twin and DNA heritability estimates for childhood behavior problems as rated by parents, teachers, and children themselves. Method Behavior problem data from 2,500 UK-representative 12-year-old twin pairs were used in twin analyses; DNA analyses were based on 1 member of the twin pair with genotype data for 1.7 million DNA markers. Diverse behavior problems were assessed, including autistic, depressive, and hyperactive symptoms. Genetic influence from DNA was estimated using genome-wide complex trait analysis (GCTA), and the twin estimates of heritability were based on standard twin model fitting. Results Behavior problems in childhood—whether rated by parents, teachers, or children themselves—show no significant genetic influence using GCTA, even though twin study estimates of heritability are substantial in the same sample, and even though both GCTA and twin study estimates of genetic influence are substantial for cognitive and anthropometric traits. Conclusions We suggest that this new type of “missing heritability,” that is, the gap between GCTA and twin study estimates for behavior problems in childhood, is due to nonadditive genetic influence, which will make it more difficult to identify genes responsible for heritability. PMID:24074471

Heritability and Temporal Stability of Ambulatory Autonomic Stress Reactivity in Unstructured 24-Hour Recordings.

PubMed

Neijts, Melanie; van Lien, Rene; Kupper, Nina; Boomsma, Dorret; Willemsen, Gonneke; de Geus, Eco J C

2015-10-01

Measurements of ambulatory autonomic reactivity can help with our understanding of the long-term health consequences of exposure to psychosocial stress in real-life settings. In this study, unstructured 24-hour ambulatory recordings of cardiac parasympathetic and sympathetic control were obtained in 1288 twins and siblings, spanning both work time and leisure time. These data were used to define two ambulatory baseline (sleep, leisure) and four stress conditions (wake, work, work_sitting, work_peak) from which six ambulatory stress reactivity measures were derived. The use of twin families allowed for estimation of heritability and testing for the amplification of existing or emergence of new genetic variance during stress compared with baseline conditions. Temporal stability of ambulatory reactivity was assessed in 62 participants and was moderate to high over a 3-year period (0.36 < r < 0.91). Depending on the definition of ambulatory reactivity used, significant heritability was found, ranging from 29% to 40% for heart rate, 34% to 47% for cardiac parasympathetic control (indexed as respiratory sinus arrhythmia), and 10% to 19% for cardiac sympathetic control (indexed as the preejection period). Heritability of ambulatory reactivity was largely due to newly emerging genetic variance during stress compared with periods of rest. Interestingly, reactivity to short standardized stressors was poorly correlated with the ambulatory reactivity measures implying poor laboratory-real-life correspondence. Ambulatory autonomic reactivity extracted from an unstructured real-life setting shows reliable, stable, and heritable individual differences. Real-life situations uncover a new and different genetic variation compared with that seen in resting baseline conditions, including sleep.

Repeatable and heritable behavioural variation in a wild cooperative breeder

PubMed Central

Burke, Terry; Dugdale, Hannah L.

2017-01-01

Abstract Quantifying consistent differences in behaviour among individuals is vital to understanding the ecological and evolutionary significance of animal personality. To quantify personality, the phenotypic variation of a behavioural trait is partitioned to assess how it varies among individuals, which is also known as repeatability. If pedigree data are available, the phenotypic variation can then be further partitioned to estimate the additive genetic variance and heritability. Assessing the repeatability and heritability of personality traits therefore allows for a better understanding of what natural selection can act upon, enabling evolution. In a natural population of facultative cooperatively breeding Seychelles warbler (Acrocephalus sechellensis) on Cousin Island, a lack of breeding vacancies forces individuals into different life-history strategies, and these differences in reproductive state could generate behavioural differences among individuals in the population. We used this population to estimate the repeatability of 4 behavioural traits (novel environment exploration, novel object exploration, obstinacy/struggle rate, and escape response), and narrow-sense heritability (of behavior, h2B; behavior minus observer variance; and personality), and evolvability, of the repeatable behavioural traits. We also tested for an among-individual correlation between the repeatable traits. We found that, compared to estimates in other study species, the exploratory behaviours were moderately repeatable (0.23–0.37), there was a positive among-individual correlation (0.51) between novel environment and novel object exploration, and that novel environment exploration was moderately heritable (0.17; h2B was low as it includes observer variance). This study further clarifies the additive genetic variance available for selection to act upon in this cooperatively breeding bird. PMID:29622921

Prevalence and heritability of psoriasis and benign migratory glossitis in one Brazilian population*

PubMed Central

Jorge, Maria Augusta; Gonzaga, Heron Fernando de Sousa; Tomimori, Jane; Picciani, Bruna Lavinas Sayed; Barbosa, Calógeras Antônio

2017-01-01

Background An oral condition associated to psoriasis is benign migratory glossitis. The review of the literature does not show any publication about heritability in both soriasis and benign migratory glossitis and prevalence of psoriasis in the Brazilian population. Objective This research was carried out in order to determine the prevalence of psoriasis and benign migratory glossitis in the Brazilian population from a Brazilian sample, as well as the heritability in these conditions. Methods Six thousand patients were studied from the records of the outpatient dermatology department. The sample had 129 patients with cutaneous psoriasis, 399 with benign migratory glossitis without psoriasis and a control group with 5,472 patients. After data collection, the statistical analysis was made using Woolf, Chi-square and Falconer tests. Results The prevalence of psoriasis was 2.15% and the benign migratory glossitis was 7.0%. The prevalence of benign migratory glossitis in the psoriasis group was high (16.3%), and that was statistically significant. Family history in the psoriasis group was 38% for the condition itself and 2,75% for benign migratory glossitis and in the benign migratory glossitis group was 17.54% for the condition itself and 1.5% for psoriasis. The study of heritability was 38.8% for psoriasis and 36.6% for benign migratory glossitis, both with medium heritability. Study limitations This study was only in the state of São Paulo. Conclusion This is the first publication that quantifies how much of these conditions have a genetic background and how important the environmental factors are in triggering them. PMID:29364438

Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs.

PubMed

Rankinen, Tuomo; Sung, Yun Ju; Sarzynski, Mark A; Rice, Treva K; Rao, D C; Bouchard, Claude

2012-03-01

Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with heart rate training responses have been identified. The purpose of our study was to perform a genome-wide association study to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 W (HR50) on 2 separate days before and after a 20-wk endurance training program in 483 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study analyses, which were performed using the MERLIN software package (single-SNP analyses and conditional heritability tests) and standard regression models (multivariate analyses). The strongest associations for HR50 training response adjusted for age, sex, body mass index, and baseline HR50 were detected with SNPs at the YWHAQ locus on chromosome 2p25 (P = 8.1 × 10(-7)), the RBPMS locus on chromosome 8p12 (P = 3.8 × 10(-6)), and the CREB1 locus on chromosome 2q34 (P = 1.6 × 10(-5)). In addition, 37 other SNPs showed P values <9.9 × 10(-5). After removal of redundant SNPs, the 10 most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability tests showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions, as well as cardiac memory formation, fully account for the heritability of the submaximal heart rate training response.

Intra-familial aggregation and heritability of aortic versus brachial pulse pressure after imputing pretreatment values in a community of African ancestry.

PubMed

Redelinghuys, Michelle; Norton, Gavin R; Maseko, Muzi J; Majane, Olebogeng H I; Woodiwiss, Angela J

2012-06-01

To compare the intra-familial aggregation and heritability of central (aortic) (PPc) versus peripheral (brachial) (PPp) pulse pressure after imputing pretreatment blood pressures (BPs) in treated participants in a community of black African ancestry. Central PPc [generalized transfer function (GTF) and radial P2-derived] was determined with applanation tonometry at the radial artery (SphygmoCor software) in 946 participants from 258 families with 23 families including three generations from an urban developing community of black Africans. In the 24.1% of participants receiving antihypertensive treatment, pretreatment brachial BP was imputed from published overall averaged effects of therapy grouped by class and dose, specific for groups of black African descent. From these data PPc was estimated from proportionate differences in central aortic and brachial PP. Heritability estimates were determined from SAGE software. Echocardiography was evaluated in 507 participants in order to determine stroke volume. With adjustments for confounders, parent-child (P < 0.05) and sibling-sibling (P < 0.0005) correlations were noted for log PPc, whilst for log PPp only sibling-sibling correlations were noted. No mother-father correlations were noted for either PPc or PPp. Independent of confounders the heritability for log GTF-derived (h = 0.33 ± 0.07, P < 0.0001) and P2-derived (h = 0.30 ± 0.07, P < 0.0001) PPc was greater than the heritability for log PPp (h = 0.11 ± 0.06, P < 0.05) (P < 0.05 for comparison of heritability estimates). After imputing pretreatment BP values, central aortic PP is significantly more inherited than brachial PP. These data suggest that in groups of African descent the genetic determinants of PP may be underestimated when employing brachial rather than central aortic PP measurements.

Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs

PubMed Central

Sung, Yun Ju; Sarzynski, Mark A.; Rice, Treva K.; Rao, D. C.; Bouchard, Claude

2012-01-01

Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with heart rate training responses have been identified. The purpose of our study was to perform a genome-wide association study to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 W (HR50) on 2 separate days before and after a 20-wk endurance training program in 483 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study analyses, which were performed using the MERLIN software package (single-SNP analyses and conditional heritability tests) and standard regression models (multivariate analyses). The strongest associations for HR50 training response adjusted for age, sex, body mass index, and baseline HR50 were detected with SNPs at the YWHAQ locus on chromosome 2p25 (P = 8.1 × 10−7), the RBPMS locus on chromosome 8p12 (P = 3.8 × 10−6), and the CREB1 locus on chromosome 2q34 (P = 1.6 × 10−5). In addition, 37 other SNPs showed P values <9.9 × 10−5. After removal of redundant SNPs, the 10 most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability tests showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions, as well as cardiac memory formation, fully account for the heritability of the submaximal heart rate training response. PMID:22174390

Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles.

PubMed

Tedeschi, J N; Kennington, W J; Tomkins, J L; Berry, O; Whiting, S; Meekan, M G; Mitchell, N J

2016-01-13

The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments. © 2016 The Author(s).

Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes.

PubMed

Rietschel, Liz; Streit, Fabian; Zhu, Gu; McAloney, Kerrie; Frank, Josef; Couvy-Duchesne, Baptiste; Witt, Stephanie H; Binz, Tina M; McGrath, John; Hickie, Ian B; Hansell, Narelle K; Wright, Margaret J; Gillespie, Nathan A; Forstner, Andreas J; Schulze, Thomas G; Wüst, Stefan; Nöthen, Markus M; Baumgartner, Markus R; Walker, Brian R; Crawford, Andrew A; Colodro-Conde, Lucía; Medland, Sarah E; Martin, Nicholas G; Rietschel, Marcella

2017-11-10

Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

PubMed Central

Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

2015-01-01

While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles

PubMed Central

Kennington, W. J.; Tomkins, J. L.; Berry, O.; Whiting, S.; Meekan, M. G.; Mitchell, N. J.

2016-01-01

The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments. PMID:26763709

Does Parental Divorce Moderate the Heritability of Body Dissatisfaction? An Extension of Previous Gene-Environment Interaction Effects

PubMed Central

O’Connor, Shannon M.; Klump, Kelly L.; VanHuysse, Jessica L.; McGue, Matt; Iacono, William

2015-01-01

Objective Previous research suggests that parental divorce moderates genetic influences on body dissatisfaction. Specifically, the heritability of body dissatisfaction is higher in children of divorced versus intact families, suggesting possible gene-environment interaction effects. However, prior research is limited to a single, self-report measure of body dissatisfaction. The primary aim of the present study was to examine whether these findings extend to a different dimension of body dissatisfaction, body image perceptions. Method Participants were 1,534 female twins from the Minnesota Twin Family Study, ages 16–20 years. The Body Rating Scale (BRS) was used to assess body image perceptions. Results Although BRS scores were heritable in twins from divorced and intact families, the heritability estimates in the divorced group were not significantly greater than estimates in the intact group. However, there were differences in nonshared environmental effects, where the magnitude of these environmental influences was larger in the divorced as compared to the intact families. Discussion Different dimensions of body dissatisfaction (i.e., negative self-evaluation versus body image perceptions) may interact with environmental risk, such as parental divorce, in discrete ways. Future research should examine this possibility and explore differential gene x environment interactions using diverse measures. PMID:26314278

Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in wheat.

PubMed

Gao, Lihong; Diarso, Moussa; Zhang, Ai; Zhang, Huakun; Dong, Yuzhu; Liu, Lixia; Lv, Zhenling; Liu, Bao

2016-01-01

Aneuploidy causes changes in gene expression and phenotypes in all organisms studied. A previous study in the model plant Arabidopsis thaliana showed that aneuploidy-generated phenotypic changes can be inherited to euploid progenies and implicated an epigenetic underpinning of the heritable variations. Based on an analysis by amplified fragment length polymorphism and methylation-sensitive amplified fragment length polymorphism markers, we found that although genetic changes at the nucleotide sequence level were negligible, extensive changes in cytosine DNA methylation patterns occurred in all studied homeologous group 1 whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with monosomic 1A showing the greatest amount of methylation changes. The changed methylation patterns were inherited by euploid progenies derived from the aneuploid parents. The aneuploidy-induced DNA methylation alterations and their heritability were verified at selected loci by bisulfite sequencing. Our data have provided empirical evidence supporting earlier suggestions that heritability of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A - was able to cause significant epigenetic divergence of the aneuploid plants and their euploid progenies also lends support to recent suggestions that aneuploidy may have played an important and protracted role in polyploid genome evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

A genome-wide assessment of rare copy number variants in colorectal cancer.

PubMed

Li, Zhenli; Yu, Dan; Gan, Meifu; Shan, Qiaonan; Yin, Xiaoyang; Tang, Shunli; Zhang, Shuai; Shi, Yongyong; Zhu, Yimin; Lai, Maode; Zhang, Dandan

2015-09-22

Colorectal cancer (CRC) is a complex disease with an estimated heritability of approximately 35%. However, known CRC-related common single nucleotide polymorphisms (SNPs) can only explain ~0.65% of the heritability. This "missing heritability" may be explained partially by rare copy number variants (CNVs). In this study, we performed a genome-wide scan using Illumina Human-Omni Express BeadChip, 694 sporadic CRC cases and 1641 controls were eventually included in our analysis after quality control. The global burden analysis revealed a 1.53-fold excess of rare CNVs in CRC cases compared with controls (P < 1 × 10(-6)), and the difference being more pronounced for genic rare CNVs and CNVs overlapped with coding regions (1.65-fold and 1.84-fold, respectively, both P < 1 × 10(-6)). Interestingly, both the cases in the lowest and middle tertile of age carried a higher burden of rare CNVs comparing to the highest tertile. Furthermore, 639 CNV-disrupted genes exclusive to CRC cases were found to be significantly enriched in gene ontology (GO) terms concerning nucleosome assembly and olfactory receptor activity. Our study was the first to evaluate the burden of rare CNVs in sporadic CRC and suggested that rare CNVs contributed to the missing heritability of CRC.

The genetic architecture of economic and political preferences

PubMed Central

Benjamin, Daniel J.; Cesarini, David; van der Loos, Matthijs J. H. M.; Dawes, Christopher T.; Koellinger, Philipp D.; Magnusson, Patrik K. E.; Chabris, Christopher F.; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M.

2012-01-01

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic–based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs. PMID:22566634

Does parental divorce moderate the heritability of body dissatisfaction? An extension of previous gene-environment interaction effects.

PubMed

O'Connor, Shannon M; Klump, Kelly L; VanHuysse, Jessica L; McGue, Matt; Iacono, William

2016-02-01

Previous research suggests that parental divorce moderates genetic influences on body dissatisfaction. Specifically, the heritability of body dissatisfaction is higher in children of divorced versus intact families, suggesting possible gene-environment interaction effects. However, prior research is limited to a single, self-reported measure of body dissatisfaction. The primary aim of this study was to examine whether these findings extend to a different dimension of body dissatisfaction: body image perceptions. Participants were 1,534 female twins from the Minnesota Twin Family Study, aged 16-20 years. The Body Rating Scale (BRS) was used to assess body image perceptions. Although BRS scores were heritable in twins from divorced and intact families, the heritability estimates in the divorced group were not significantly greater than estimates in the intact group. However, there were differences in nonshared environmental effects, where the magnitude of these environmental influences was larger in the divorced as compared with the intact families. Different dimensions of body dissatisfaction (i.e., negative self-evaluation versus body image perceptions) may interact with environmental risk, such as parental divorce, in discrete ways. Future research should examine this possibility and explore differential gene-environment interactions using diverse measures. © 2015 Wiley Periodicals, Inc.

The genetic architecture of economic and political preferences.

PubMed

Benjamin, Daniel J; Cesarini, David; van der Loos, Matthijs J H M; Dawes, Christopher T; Koellinger, Philipp D; Magnusson, Patrik K E; Chabris, Christopher F; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M

2012-05-22

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic-based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs.

Heritability of Problem Drinking and the Genetic Overlap with Personality in a General Population Sample

PubMed Central

de Moor, Marleen H. M.; Vink, Jacqueline M.; van Beek, Jenny H. D. A.; Geels, Lot M.; Bartels, Meike; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.

2011-01-01

This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. In a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items) and personality [NEO Five-Factor Inventory (FFI); 60 items] were collected in 2009/2010 by surveys. Confirmatory factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r = 0.74) underlying factors. A higher-order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE, which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to −0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32 and 55%, and some evidence for non-additive genetic influences) were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12| and |0.41|). Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality. PMID:22303371

Environmental and Genetic Contribution to Hypertension Prevalence: Data from an Epidemiological Survey on Sardinian Genetic Isolates

PubMed Central

Biino, Ginevra; Parati, Gianfranco; Concas, Maria Pina; Adamo, Mauro; Angius, Andrea; Vaccargiu, Simona; Pirastu, Mario

2013-01-01

Background and Objectives Hypertension represents a major cause of cardiovascular morbidity and mortality worldwide but its prevalence has been shown to vary in different countries. The reasons for such differences are still matter of debate, the relative contributions given by environmental and genetic factors being still poorly defined. We estimated the current prevalence, distribution and determinants of hypertension in isolated Sardinian populations and also investigated the environmental and genetic contribution to hypertension prevalence taking advantage of the characteristics of such populations. Methods and Results An epidemiological survey with cross-sectional design was carried out measuring blood pressure in 9845 inhabitants of 10 villages of Ogliastra region between 2002 and 2008. Regression analysis for assessing blood pressure determinants and variance component models for estimating heritability were performed. Overall 38.8% of this population had hypertension, its prevalence varying significantly by age, sex and among villages taking into account age and sex structure of their population. About 50% of hypertensives had prior cardiovascular disease. High blood pressure was independently associated with age, obesity related factors, heart rate, total cholesterol, alcohol consumption, low education and smoking status, all these factors contributing more in women than in men. Heritability was 27% for diastolic and 36% for systolic blood pressure, its contribution being significantly higher in men (57%) than in women (46%). Finally, the genetic correlation between systolic and diastolic blood pressure was 0.74, indicating incomplete pleiotropy. Conclusion Genetic factors involved in the expression of blood pressure traits account for about 30% of the phenotypic variance, but seem to play a larger role in men; comorbidities and environmental factors remain of predominant importance, but seem to contribute much more in women. PMID:23527229

Genetic variation and correlated changes in reproductive performance of a red tilapia line selected for improved growth over three generations.

PubMed

Thoa, Ngo Phu; Hamzah, Azhar; Nguyen, Nguyen Hong

2017-09-01

The present study examines genetic variation and correlated changes in reproductive performance traits in a red tilapia (Oreochromis spp.) population selected over three generations for improved growth. A total of 328 breeding females (offspring of 111 sires and 118 dams) had measurements of body weight prior to spawning (WBS), number of fry at hatching (NFH), total fry weight (TFW) and number of dead fry (NDF) or mortality of fry including unhatched eggs at hatching (MFH). Restricted maximum likelihood (REML) analysis in a multi-trait model showed that there are heritable genetic components for all traits studied. The heritability for WBS was very high (0.80). The estimates for traits related to fecundity (NFH, TFW) and survival (NDF) were low and they were associated with high standard errors. Genetic correlations of WBS with other reproductive performance traits (NFH, TFW and NDF) were generally positive. However, NFH was negatively correlated genetically with TFW. As expected, body measurements during growth stage exhibited strong positive genetic correlations with WBS. The genetic correlations between body traits and reproductive performance (NFH, TFW, NDF) were not significant. Correlated responses in reproductive traits were measured as changes in least squares means between generations or spawning years. Except for WBS that increased with the selection programs, the phenotypic changes in other reproductive traits observed were not statistically significant (P>0.05). It is concluded that the selection program for red tilapia has resulted in very little changes in reproductive performance of the animals after three generations. However, periodic monitoring of genetic changes in fecundity and fitness related traits such as NDF or MFH should be made in selective breeding programs for red tilapia. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

PubMed Central

Morrison, Jean; Laurie, Cathy C.; Marazita, Mary L.; Sanders, Anne E.; Offenbacher, Steven; Salazar, Christian R.; Conomos, Matthew P.; Thornton, Timothy; Jain, Deepti; Laurie, Cecelia A.; Kerr, Kathleen F.; Papanicolaou, George; Taylor, Kent; Kaste, Linda M.; Beck, James D.; Shaffer, John R.

2016-01-01

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata. PMID:26662797

Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

PubMed Central

Duan, Shiwei; Bleibel, Wasim K.; Huang, Rong Stephanie; Shukla, Sunita J.; Wu, Xiaolin; Badner, Judith A.; Dolan, M. Eileen

2009-01-01

Daunorubicin is an anthracycline antibiotic agent used in the treatment of hematopoietic malignancies. Toxicities associated with this agent include myelosuppression and cardiotoxicity; however, the genes or genetic determinants that contribute to these toxicities are unknown. We present an unbiased genome-wide approach that incorporates heritability, whole-genome linkage analysis, and linkage-directed association to uncover genetic variants contributing to the sensitivity to daunorubicin-induced cytotoxicity. Cell growth inhibition in 324 Centre d’ Etude du Polymorphisme Humain lymphoblastoid cell lines (24 pedigrees) was evaluated following treatment with daunorubicin for 72 h. Heritability analysis showed a significant genetic component contributing to the cytotoxic phenotypes (h2 = 0.18–0.63at 0.0125, 0.025, 0.05, 0.1, 0.2, and 1.0 µmol/L daunorubicin and at the IC50, the dose required to inhibit 50% cell growth). Whole-genome linkage scans at all drug concentrations and IC50 uncovered 11 regions with moderate peak LOD scores (>1.5), including 4q28.2 to 4q32.3 with a maximum LOD score of 3.18. The quantitative transmission disequilibrium tests were done using 31,312 high-frequency single-nucleotide polymorphisms (SNP) located in the 1 LOD confidence interval of these 11 regions. Thirty genes were identified as significantly associated with daunorubicin-induced cytotoxicity (P ≤ 2.0 × 10−4, false discovery rate ≤ 0.1). Pathway and functional gene ontology analysis showed that these genes were overrepresented in the phosphatidylinositol signaling system, axon guidance pathway, and GPI-anchored proteins family. Our findings suggest that a proportion of susceptibility to daunorubicin-induced cytotoxicity may be controlled by genetic determinants and that analysis using linkage-directed association studies with dense SNP markers can be used to identify the genetic variants contributing to cytotoxicity. PMID:17545624

Six low-penetrance SNPs for the estimation of breast cancer heritability: A family-based study in Caucasian Italian patients

PubMed Central

De Summa, Simona; Graziano, Francesca; Pilato, Brunella; Pinto, Rosamaria; Danza, Katia; Lacalamita, Rosanna; Serratì, Simona; Sambiasi, Domenico; Grassi, Mario; Tommasi, Stefania

2017-01-01

Breast cancer is a malignancy with a strong heritable component. Genetic counseling has been principally focused on families carrying high-penetrance breast cancer 1/2, early onset genes. Current modeling suggests that the majority of the unexplained fraction of familial risk is likely to be explained by a polygenic model. The aim of the present study was to estimate the heritability (h2) of breast cancer susceptibility through the analysis of 6 single nucleotide polymorphisms (SNPs), nuclear mitotic apparatus protein 1, cyclin D1, cytochrome C oxidase copper chaperone, fibroblast growth factor receptor 2, TOX high mobility group box family member 3 and solute carrier family 4 member 7. These 6 SNPs, previously identified by genome-wide association studies, were considered to evaluate the additive and common environmental components that contribute to the development of breast cancer in nuclear (pedigrees including only first degree relationships) and in extended families (with at most third degree relationships). A total of 22 extended pedigrees, subsequently split into 52 nuclear pedigrees were analyzed. An example of splitting process from extended to nuclear pedigree is shown in Fig. 1. Firstly, an underline latent continuous trait (Y*) using breast cancer status and information of 6 breast cancer-associated SNPs was calculated. This novel trait summarized the susceptibility of breast cancer in each individual. Secondly, the h2 of Y* was estimated using an additive polygenic-common environment-unique error model. h2 was evaluated in extended and immediate pedigrees, obtaining comparable results. h2 accounts for ~40% of the total phenotypic variance, indicating a fairly strong additive genetic effect of breast cancer susceptibility. The present study indicated the importance of the evaluation and consideration of these six SNPs, which can be used as instrumental variables in order to obtain improved genetic models that are useful for h2 analysis. PMID:28943953

Estimation of genetic parameters and response to selection for a continuous trait subject to culling before testing.

PubMed

Arnason, T; Albertsdóttir, E; Fikse, W F; Eriksson, S; Sigurdsson, A

2012-02-01

The consequences of assuming a zero environmental covariance between a binary trait 'test-status' and a continuous trait on the estimates of genetic parameters by restricted maximum likelihood and Gibbs sampling and on response from genetic selection when the true environmental covariance deviates from zero were studied. Data were simulated for two traits (one that culling was based on and a continuous trait) using the following true parameters, on the underlying scale: h² = 0.4; r(A) = 0.5; r(E) = 0.5, 0.0 or -0.5. The selection on the continuous trait was applied to five subsequent generations where 25 sires and 500 dams produced 1500 offspring per generation. Mass selection was applied in the analysis of the effect on estimation of genetic parameters. Estimated breeding values were used in the study of the effect of genetic selection on response and accuracy. The culling frequency was either 0.5 or 0.8 within each generation. Each of 10 replicates included 7500 records on 'test-status' and 9600 animals in the pedigree file. Results from bivariate analysis showed unbiased estimates of variance components and genetic parameters when true r(E) = 0.0. For r(E) = 0.5, variance components (13-19% bias) and especially (50-80%) were underestimated for the continuous trait, while heritability estimates were unbiased. For r(E) = -0.5, heritability estimates of test-status were unbiased, while genetic variance and heritability of the continuous trait together with were overestimated (25-50%). The bias was larger for the higher culling frequency. Culling always reduced genetic progress from selection, but the genetic progress was found to be robust to the use of wrong parameter values of the true environmental correlation between test-status and the continuous trait. Use of a bivariate linear-linear model reduced bias in genetic evaluations, when data were subject to culling. © 2011 Blackwell Verlag GmbH.

Heritability of levels of autoantibodies using the method of plotting regression of offspring on midparent (ROMP).

PubMed

Outschoorn, Ingrid M; Rose, Noel R; Burek, C Lynne; Jones, Tim W; Mackay, Ian R; Rowley, Merrill J

2005-06-01

The genetic control of the levels of autoantibodies has rarely been examined. We examined the heritability of autoantibodies to glutamic acid decarboxylase (GAD65) in type 1 diabetes, and to thyroglobulin (Tg) in chronic lymphocytic thyroiditis and thyrotoxicosis, using regression of offspring on midparent (ROMP) methods. Levels of autoantibodies in patients and their parents were significantly correlated in thyrotoxicosis (R2 = 0.569, p = 0.001), consistent with the reported Gm association, but not in chronic lymphocytic thyroiditis or type 1 diabetes. Extension of the procedure to other autoantibody disorders could be informative.

From observational to dynamic genetics

PubMed Central

Haworth, Claire M. A.; Davis, Oliver S. P.

2014-01-01

Twin and family studies have shown that most traits are at least moderately heritable. But what are the implications of finding genetic influence for the design of intervention and prevention programs? For complex traits, heritability does not mean immutability, and research has shown that genetic influences can change with age, context, and in response to behavioral and drug interventions. The most significant implications for intervention will come when we move from observational genetics to investigating dynamic genetics, including genetically sensitive interventions. Future interventions should be designed to overcome genetic risk and draw upon genetic strengths by changing the environment. PMID:24478793

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

PubMed Central

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Cardona Silgado, Julio C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Walkup, John; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G.M.; Yao, Yin; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

2014-01-01

Obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS) are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. Here, we report a combined genome-wide association study (GWAS) of TS and OCD in 2723 cases (1310 with OCD, 834 with TS, 579 with OCD plus TS/chronic tics (CT)), 5667 ancestry-matched controls, and 290 OCD parent-child trios. Although no individual single nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels, i.e. expression quantitative loci (eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10−4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, TS had a smaller, non-significant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and TS/CT were included in the analysis (p=0.01). Previous work has shown that TS and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of TS and OCD. Furthermore, OCD with co-occurring TS/CT may have different underlying genetic susceptibility compared to OCD alone. PMID:25158072

Differential heritability of adult and juvenile antisocial traits.

PubMed

Lyons, M J; True, W R; Eisen, S A; Goldberg, J; Meyer, J M; Faraone, S V; Eaves, L J; Tsuang, M T

1995-11-01

Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We compared DSM-III-R antisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. We administered the Diagnostic Interview Schedule Version III-revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile anti-social traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

Heritability of the severity of diabetic retinopathy: the FIND-Eye study.

PubMed

Arar, Nedal H; Freedman, Barry I; Adler, Sharon G; Iyengar, Sudha K; Chew, Emily Y; Davis, Mathew D; Satko, Scott G; Bowden, Donald W; Duggirala, Ravi; Elston, Robert C; Guo, Xiuxing; Hanson, Robert L; Igo, Robert P; Ipp, Eli; Kimmel, Paul L; Knowler, William C; Molineros, Julio; Nelson, Robert G; Pahl, Madeleine V; Quade, Shannon R E; Rasooly, Rebekah S; Rotter, Jerome I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Zager, Philip G; Abboud, Hanna E

2008-09-01

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection.

Heritability of the Severity of Diabetic Retinopathy: The FIND-Eye Study

PubMed Central

Arar, Nedal H.; Freedman, Barry I.; Adler, Sharon G.; Iyengar, Sudha K.; Chew, Emily Y.; Davis, Mathew D.; Satko, Scott G.; Bowden, Donald W.; Duggirala, Ravi; Elston, Robert C.; Guo, Xiuxing; Hanson, Robert L.; Igo, Robert P.; Ipp, Eli; Kimmel, Paul L.; Knowler, William C.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeleine V.; Quade, Shannon R. E.; Rasooly, Rebekah S.; Rotter, Jerome I.; Saad, Mohammed F.; Scavini, Marina; Schelling, Jeffrey R.; Sedor, John R.; Shah, Vallabh O.; Zager, Philip G.; Abboud, Hanna E.

2008-01-01

PURPOSE Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. METHODS The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib–sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. RESULTS This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (χ2 = 658.14, df = 20; P < 0.0001). The sib–sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. CONCLUSIONS These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection. PMID:18765632

Bilaterally Asymmetric Effects of Quantitative Trait Loci (QTLs): QTLs That Affect Laxity in the Right Versus Left Coxofemoral (Hip) Joints of the Dog (Canis familiaris)

PubMed Central

Chase, Kevin; Lawler, Dennis F.; Adler, Fred R.; Ostrander, Elaine A.; Lark, Karl G.

2009-01-01

In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint.A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxity. A significant directed asymmetry was observed, such that greater laxity was observed in the left than the right hip. This asymmetry was not heritable. However, the average Norberg angle was highly heritable as were the Norberg angles of either the right or left hips. After correction for pedigree effects, two QTLs were identified using the metrics of the left and right hips as separate data sets. Both are on canine chromosome 1 (CFA1), separated by about 95 Mb. One QTL, associated with the SSR marker FH2524 was significant for the left, but not the right hip. The other, associated with FH2598, was significant for the right but not the left hip. For both QTLs, some extreme phenotypes were best explained by specific interactions between haplotypes. PMID:14708095

Bilaterally asymmetric effects of quantitative trait loci (QTLs): QTLs that affect laxity in the right versus left coxofemoral (hip) joints of the dog (Canis familiaris).

PubMed

Chase, Kevin; Lawler, Dennis F; Adler, Fred R; Ostrander, Elaine A; Lark, Karl G

2004-01-30

In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint. A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxity. A significant directed asymmetry was observed, such that greater laxity was observed in the left than the right hip. This asymmetry was not heritable. However, the average Norberg angle was highly heritable as were the Norberg angles of either the right or left hips. After correction for pedigree effects, two QTLs were identified using the metrics of the left and right hips as separate data sets. Both are on canine chromosome 1 (CFA1), separated by about 95 Mb. One QTL, associated with the SSR marker FH2524 was significant for the left, but not the right hip. The other, associated with FH2598, was significant for the right but not the left hip. For both QTLs, some extreme phenotypes were best explained by specific interactions between haplotypes. Copyright 2003 Wiley-Liss, Inc.

A systematic review of the heritability of specific psychopathic traits using Hare's two-factor model of psychopathy.

PubMed

Dhanani, Sapna; Kumari, Veena; Puri, Basant K; Treasaden, Ian; Young, Susan; Sen, Piyal

2018-02-01

There have been no systematic reviews that investigated the heritability of the two-factor model of psychopathy: interpersonal-affective and behavioral. Our review aimed, first, to examine the heritability of general psychopathic traits and, second, if genetic influences were suggested, to determine the heritability of various traits related to the interpersonal-affective and behavioral factors of psychopathy. A systematic literature search was conducted using articles from the PsycINFO, Embase, Global Health, Medline, PubMed, Web of Science, and Scopus databases (January of 1980 to December of 2015) in order to identify eligible literature that reported on the heritability of psychopathy-related traits. Papers were also found via manual examination and reference tracking. Papers were subjected to exclusion criteria and quality appraisal. We identified a total of 24 studies. Our results were grouped into three categories: general, interpersonal-affective, and behavioral. All these areas demonstrated modest to high heritability. The highest heritability values were found in studies investigating callous-unemotional behaviors. Heritability was found for all the psychopathic traits. Future research should include endophenotypic approaches that explore gene-environment correlations, which could aid in identification of the behavioral phenotype that is most amenable to early intervention by way of moderation of genetic risk.

Genetic and environmental factors affecting perinatal and preweaning survival of D'man lambs.

PubMed

Boujenane, Ismaïl; Chikhi, Abdelkader; Lakcher, Oumaïma; Ibnelbachyr, Mustapha

2013-08-01

This study examined the viability of 4,554 D'man lambs born alive at Errachidia research station in south-eastern Morocco between 1988 and 2009. Lamb survival to 1, 10, 30 and 90 days old was 0.95, 0.93, 0.93 and 0.92, respectively. The majority of deaths (85.7%) occurred before 10 days of age. Type and period of birth both had a significant effect on lamb survival traits, whereas age of dam and sex of lamb did not. The study revealed a curvilinear relationship between lamb's birth weight and survival traits from birth to 90 days, with optimal birth weights for maximal perinatal and preweaning survival varying according to type of birth from 2.6 to 3.5 kg. Estimation of variance components, using an animal model including direct and maternal genetic effects, the permanent maternal environment as well as fixed effects, showed that direct and maternal heritability estimates for survival traits between birth and 90 days were mostly low and varied from 0.01 to 0.10; however, direct heritability for survival at 1 day from birth was estimated at 0.63. Genetic correlations between survival traits and birth weight were positive and low to moderate. It was concluded that survival traits of D'man lambs between birth and 90 days could be improved through selection, but genetic progress would be low. However, the high proportion of the residual variance to total variance reinforces the need to improve management and lambing conditions.

A twin study of the genetics of fear conditioning.

PubMed

Hettema, John M; Annas, Peter; Neale, Michael C; Kendler, Kenneth S; Fredrikson, Mats

2003-07-01

Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.

Non-Mendelian determinants of morphology in fungi.

PubMed

Malagnac, Fabienne; Silar, Philippe

2003-12-01

Morphological plasticity is a hallmark of eumycetes. In addition to genes and environment, epigenetic factors control cell, colony and thallus forms in many species, by creating reversible switches. Current knowledge indicates that the different shapes are due to structural or regulatory heritable states of cytoplasmic components. Cellular physiology differs in the various forms, permitting adaptation to fluctuation in the environment. These switches are part of the adaptation repertoire that fungi exhibit to colonize most niches.

Heritability of Pain Catastrophizing and Associations with Experimental Pain Outcomes: A Twin Study

PubMed Central

Trost, Zina; Strachan, Eric; Sullivan, Michael; Vervoort, Tine; Avery, Ally R.; Afari, Niloofar

2014-01-01

The current study employed a twin paradigm to examine the genetic and environmental contributions to pain catastrophizing as well as the observed association between pain catastrophizing and cold pressor task (CPT) outcomes. Male and female monozygotic (n=206) and dizygotic twins (n=194) from the University of Washington Twin Registry completed a measure of pain catastrophizing and performed a CPT challenge. As expected, pain catastrophizing emerged as a significant predictor of several CPT outcomes, including cold pressor immersion tolerance, pain tolerance, and delayed pain rating. The heritability estimate for pain catastrophizing was found to be 37% with the remaining 63% of variance attributable to unique environmental influence. Additionally, the observed associations between pain catastrophizing and CPT outcomes were not found attributable to shared genetics or environmental exposure, suggesting a direct relationship between catastrophizing and experimental pain outcomes. This study is the first to examine the heritability of pain catastrophizing and potential processes by which pain catastrophizing is related to experimental pain response. PMID:25599234

Realized heritability of personalities in the great tit (Parus major).

PubMed

Drent, Pieter J; van Oers, Kees; van Noordwijk, Arie J

2003-01-07

Behaviour under conditions of mild stress shows consistent patterns in all vertebrates: exploratory behaviour, boldness, aggressiveness covary in the same way. The existence of highly consistent individual variation in these behavioural strategies, also referred to as personalities or coping styles, allows us to measure the behaviour under standardized conditions on birds bred in captivity, link the standardized measurements to the behaviour under natural conditions and measure natural selection in the field. We have bred the great tit (Parus major), a classical model species for the study of behaviour under natural conditions, in captivity. Here, we report a realized heritability of 54 +/- 5% for early exploratory behaviour, based on four generations of bi-directional artificial selection. In addition to this, we measured hand-reared juveniles and their wild-caught parents in the laboratory. The heritability found in the mid-offspring-mid-parent regression was significantly different from zero. We have thus established the presence of considerable amounts of genetic variation for personality types in a wild bird.

Applying Biometric Growth Curve Models to Developmental Synchronies in Cognitive Development: The Louisville Twin Study.

PubMed

Finkel, Deborah; Davis, Deborah Winders; Turkheimer, Eric; Dickens, William T

2015-11-01

Biometric latent growth curve models were applied to data from the LTS in order to replicate and extend Wilson's (Child Dev 54:298-316, 1983) findings. Assessments of cognitive development were available from 8 measurement occasions covering the period 4-15 years for 1032 individuals. Latent growth curve models were fit to percent correct for 7 subscales: information, similarities, arithmetic, vocabulary, comprehension, picture completion, and block design. Models were fit separately to WPPSI (ages 4-6 years) and WISC-R (ages 7-15). Results indicated the expected increases in heritability in younger childhood, and plateaus in heritability as children reached age 10 years. Heritability of change, per se (slope estimates), varied dramatically across domains. Significant genetic influences on slope parameters that were independent of initial levels of performance were found for only information and picture completion subscales. Thus evidence for both genetic continuity and genetic innovation in the development of cognitive abilities in childhood were found.

Serotonergic genotypes, neuroticism, and financial choices.

PubMed

Kuhnen, Camelia M; Samanez-Larkin, Gregory R; Knutson, Brian

2013-01-01

Life financial outcomes carry a significant heritable component, but the mechanisms by which genes influence financial choices remain unclear. Focusing on a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR), we found that individuals possessing the short allele of this gene invested less in equities, were less engaged in actively making investment decisions, and had fewer credit lines. Short allele carriers also showed higher levels of the personality trait neuroticism, despite not differing from others with respect to cognitive skills, education, or wealth. Mediation analysis suggested that the presence of the 5-HTTLPR short allele decreased real life measures of financial risk taking through its influence on neuroticism. These findings show that 5-HTTLPR short allele carriers avoid risky and complex financial choices due to negative emotional reactions, and have implications for understanding and managing individual differences in financial choice.

Multigenerational Epigenetic Adaptation of the Hepatic Wound-Healing Response

PubMed Central

Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K.; Mathers, John C.; Fox, Christopher R.; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D.; Wilson, Caroline L.; Anstee, Quentin M.; Barter, Matt J.; Masson, Steven; Elsharkawy, Ahmed M.; Mann, Derek A.; Mann, Jelena

2012-01-01

We asked if ancestral liver damage leads to heritable reprogramming of hepatic wound-healing. We discovered that male rats with a history of liver damage transmit epigenetic suppressive adaptation of the fibrogenic component of wound-healing through male F1 and F2 generations. Underlying this adaptation was reduced generation of liver myofibroblasts, increased hepatic expression of antifibrogenic PPAR-γ and decreased expression of profibrogenic TGF-β1. Remodelling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for H2A.Z and H3K27me3 at PPAR-γ chromatin. These sperm chromatin modifications were transmittable by adaptive serum transfer from fibrotic rats and were induced in stem cells exposed to myofibroblast-conditioned media. A myofibroblast secreted soluble factor therefore stimulates heritable epigenetic signatures to sperm so as to adapt fibrogenesis in offspring. Humans with mild liver fibrosis display PPAR-γ promoter hypomethylation compared with severe fibrotics, thus lending support for epigenetic regulation of fibrosis. PMID:22941276

Genetic relations among procrastination, impulsivity, and goal-management ability: implications for the evolutionary origin of procrastination.

PubMed

Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

2014-06-01

Previous research has revealed a moderate and positive correlation between procrastination and impulsivity. However, little is known about why these two constructs are related. In the present study, we used behavior-genetics methodology to test three predictions derived from an evolutionary account that postulates that procrastination arose as a by-product of impulsivity: (a) Procrastination is heritable, (b) the two traits share considerable genetic variation, and (c) goal-management ability is an important component of this shared variation. These predictions were confirmed. First, both procrastination and impulsivity were moderately heritable (46% and 49%, respectively). Second, although the two traits were separable at the phenotypic level (r = .65), they were not separable at the genetic level (r genetic = 1.0). Finally, variation in goal-management ability accounted for much of this shared genetic variation. These results suggest that procrastination and impulsivity are linked primarily through genetic influences on the ability to use high-priority goals to effectively regulate actions. © The Author(s) 2014.

Genetic Relations Among Procrastination, Impulsivity, and Goal-Management Ability: Implications for the Evolutionary Origin of Procrastination

PubMed Central

Gustavson, Daniel E.; Miyake, Akira; Hewitt, John K.; Friedman, Naomi P.

2014-01-01

Previous research has revealed a moderate positive correlation between procrastination and impulsivity. However, little is known about why these two constructs are related. This study used behavioral genetic methodology to test three predictions derived from an evolutionary account that postulates that procrastination arose as a by-product of impulsivity (Steel, 2010): (a) Procrastination is heritable; (b) the two traits share considerable genetic variation; and (c) goal-management ability is an important component of this shared variation. These predictions were confirmed. First, both procrastination and impulsivity were moderately heritable (46% and 49%, respectively). Second, although the two traits were separable at the phenotypic level (r=.65), they were not separable at the genetic level (rg=1.0). Finally, variation in goal-management ability accounted for much of this shared genetic variation. These results suggest that procrastination and impulsivity are linked primarily through genetic influences on the ability to use their high-priority goals effectively to regulate their action. PMID:24705635

Genetic analysis of traits affecting the success of embryo transfer in dairy cattle.

PubMed

König, S; Bosselmann, F; von Borstel, U U; Simianer, H

2007-08-01

The primary aim of this study was to estimate variance components for traits related to embryo transfer (ET) by applying generalized linear mixed models (GLMM) for different distributions of traits (normal, binomial, and Poisson) in a synergistic context. Synergistic models were originally developed for traits affected by several genotypes, denoted as maternal, paternal, and direct effects. In the case of ET, the number of flushed ova (FO) only depends on a donor's maternal genetic effect, whereas paternal fertility must be considered for other embryo survival traits, such as the number of transferable embryos (TE), the number of degenerated embryos (DE), the number of unfertilized oocytes (UO), and the percentage of transferable embryos (PTE). Data for these traits were obtained from 4,196 flushes of 2,489 Holstein cows within 4 regions of northwest Germany from January 1998 through October 2004. Estimates of maternal heritability were 0.231 for FO, 0.096 for TE, 0.021 for DE, 0.135 for UO, and 0.099 for PTE, whereas the relative genetic impact of the paternal component was near zero. Estimates of the genetic correlations between the maternal and the paternal component were slightly negative, indicating a genetic antagonism. For the analysis of pregnancy after ET, 8,239 transfers to 6,819 different Holstein-Friesian recipients were considered by applying threshold methodology. The direct heritability for pregnancy in the recipient after ET was 0.056. The relative genetic impact of maternal and paternal components on pregnancy of recipients describing a donor's and a sire's ability to produce viable embryos was below 1%. The genetic correlations of the direct effect of the recipient with the sire of embryos (paternal effect) and the donor cow (maternal effect) for pregnancy after ET were -0.32 and -0.14, respectively. With the exception of FO and PTE (-0.17), estimates of genetic correlations among traits for the maternal site were distinctly positive, especially between FO and TE (0.74). Based on this high genetic correlation and due to the higher heritability for FO, indirect selection on FO will increase selection response in TE by about 22% compared with direct selection on TE. The negative genetic correlation of -0.27 between TE and lactation milk yield indicates the need for development of an index for bull dams in multiple ovulation and embryo transfer (MOET) breeding schemes combining production as well as traits related to ET.

Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome-wide association study

PubMed Central

VAIDYANATHAN, UMA; MALONE, STEPHEN M.; MILLER, MICHAEL B.; McGUE, MATT; IACONO, WILLIAM G.

2014-01-01

Acoustic startle responses have been studied extensively in relation to individual differences and psychopathology. We examined three indices of the blink response in a picture-viewing paradigm—overall startle magnitude across all picture types, and aversive and pleasant modulation scores—in 3,323 twins and parents. Biometric models and molecular genetic analyses showed that half the variance in overall startle was due to additive genetic effects. No single nucleotide polymorphism was genome-wide significant, but GRIK3 did produce a significant effect when examined as part of a candidate gene set. In contrast, emotion modulation scores showed little evidence of heritability in either biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14 did produce a significant effect for aversive modulation. We conclude that, although overall startle retains potential as an endophenotype, emotion-modulated startle does not. PMID:25387708

Avoiding pitfalls in estimating heritability with the common options approach

PubMed Central

Danchin, Etienne; Wajnberg, Eric; Wagner, Richard H.

2014-01-01

In many circumstances, heritability estimates are subject to two potentially interacting pitfalls: the spatial and the regression to the mean (RTM) fallacies. The spatial fallacy occurs when the set of potential movement options differs among individuals according to where individuals depart. The RTM fallacy occurs when extreme measurements are followed by measurements that are closer to the mean. We simulated data from the largest published heritability study of a behavioural trait, colony size choice, to examine the operation of the two fallacies. We found that spurious heritabilities are generated under a wide range of conditions both in experimental and correlative estimates of heritability. Classically designed cross-foster experiments can actually increase the frequency of spurious heritabilities. Simulations showed that experiments providing all individuals with the identical set of options, such as by fostering all offspring in the same breeding location, are immune to the two pitfalls. PMID:24865284

Development and genetics of brain temporal stability related to attention problems in adolescent twins.

PubMed

Smit, Dirk J A; Anokhin, Andrey P

2017-05-01

The brain continuously develops and reorganizes to support an expanding repertoire of behaviors and increasingly complex cognition. These processes may, however, also result in the appearance or disappearance of specific neurodevelopmental disorders such as attention problems. To investigate whether brain activity changed during adolescence, how genetics shape this change, and how these changes were related to attention problems, we measured EEG activity in 759 twins and siblings, assessed longitudinally in four waves (12, 14, 16, and 18years of age). Attention problems were assessed with the SWAN at waves 12, 14, and 16. To characterize functional brain development, we used a measure of temporal stability (TS) of brain oscillations over the recording time of 5min reflecting the tendency of a brain to maintain the same oscillatory state for longer or shorter periods. Increased TS may reflect the brain's tendency to maintain stability, achieve focused attention, and thus reduce "mind wandering" and attention problems. The results indicate that brain TS is increased across the scalp from 12 to 18. TS showed large individual differences that were heritable. Change in TS (alpha oscillations) was heritable between 12 and 14 and between 14 and 16 for the frontal brain areas. Absolute levels of brain TS at each wave were positively correlated with attention problems but not significantly. High and low attention problems subjects showed different developmental trajectories in TS, which was significant in a cluster of frontal leads. These results indicate that trajectories in brain TS development are a biomarker for the developing brain. TS in brain oscillations is highly heritable, and age-related change in TS is also heritable in selected brain areas. These results suggest that high and low attention problems subjects are at different stages of brain development. Copyright © 2016. Published by Elsevier B.V.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

PubMed

Thevenon, J; Bourredjem, A; Faivre, L; Cardot-Bauters, C; Calender, A; Le Bras, M; Giraud, S; Niccoli, P; Odou, M F; Borson-Chazot, F; Barlier, A; Lombard-Bohas, C; Clauser, E; Tabarin, A; Pasmant, E; Chabre, O; Castermans, E; Ruszniewski, P; Bertherat, J; Delemer, B; Christin-Maitre, S; Beckers, A; Guilhem, I; Rohmer, V; Goichot, B; Caron, P; Baudin, E; Chanson, P; Groussin, L; Du Boullay, H; Weryha, G; Lecomte, P; Schillo, F; Bihan, H; Archambeaud, F; Kerlan, V; Bourcigaux, N; Kuhn, J M; Vergès, B; Rodier, M; Renard, M; Sadoul, J L; Binquet, C; Goudet, P

2015-12-01

MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity. © 2015 European Society of Endocrinology.

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

PubMed Central

Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

2016-01-01

Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

Heritability of anti-predatory traits: vigilance and locomotor performance in marmots.

PubMed

Blumstein, D T; Lea, A J; Olson, L E; Martin, J G A

2010-05-01

Animals must allocate some proportion of their time to detecting predators. In birds and mammals, such anti-predator vigilance has been well studied, and we know that it may be influenced by a variety of intrinsic and extrinsic factors. Despite hundreds of studies focusing on vigilance and suggestions that there are individual differences in vigilance, there have been no prior studies examining its heritability in the field. Here, we present one of the first reports of (additive) genetic variation in vigilance. Using a restricted maximum likelihood procedure, we found that, in yellow-bellied marmots (Marmota flaviventris), the heritability of locomotor ability (h(2)=0.21), and especially vigilance (h(2) = 0.08), is low. These modest heritability estimates suggest great environmental variation or a history of directional selection eliminating genetic variation in these traits. We also found a significant phenotypic (r(P) = -0.09 +/- 0.04, P = 0.024) and a substantial, but not significant, genetic correlation (r(A) = -0.57 +/- 0.28, P = 0.082) between the two traits (slower animals are less vigilant while foraging). We found no evidence of differential survival or longevity associated with particular phenotypes of either trait. The genetic correlation may persist because of environmental heterogeneity and genotype-by-environment interactions maintaining the correlation, or because there are two ways to solve the problem of foraging in exposed areas: be very vigilant and rely on early detection coupled with speed to escape, or reduce vigilance to minimize time spent in an exposed location. Both strategies seem to be equally successful, and this 'locomotor ability-wariness' syndrome may therefore allow slow animals to compensate behaviourally for their impaired locomotor ability.

Genetic influences on heart rate variability

PubMed Central

Golosheykin, Simon; Grant, Julia D.; Novak, Olga V.; Heath, Andrew C.; Anokhin, Andrey P.

2016-01-01

Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. PMID:27114045

Molecular Etiology of Hereditary Single-Side Deafness: Its Association With Pigmentary Disorders and Waardenburg Syndrome.

PubMed

Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-10-01

Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.

Wounding response in xylem of Scots pine seedlings shows wide genetic variation and connection with the constitutive defence of heartwood.

PubMed

Harju, Anni M; Venäläinen, Martti; Laakso, Tapio; Saranpää, Pekka

2009-01-01

In this greenhouse experiment, 3-year-old Scots pine (Pinus sylvestris L.) seedlings were wounded by drilling holes through the stem. In the xylem next to the wound, the concentration of resin acids (RAC) increased, and the production of extractives typical for heartwood (stilbenes) and knotwood (stilbenes and lignans) of mature trees was induced. The induced stilbenes were pinosylvin (PS) and pinosylvin monomethyl ether (PSM), and the lignans nortrachelogenin (NTG) and matairesinol (MR). There was positive phenotypic correlation between concentrations of the different extractives. Except for the RAC, the extractive concentrations showed no correlation with the size of the seedlings. The treated seedlings belonged to half-sib families, which enabled the estimation of the genetic parameters for the response variables. The proportion of heritable variation (heritability, h(2)) in the concentration of PS, NTG and MR varied between 0.71 and 1.03, whereas for PSM and RAC the heritability was lower (0.35 and 0.31). Genetic correlation was significant between PS and PSM (r = 0.55, P = 0.018), and between NTG and MR (r = 0.50, P = 0.033). Heritabilities were also estimated on the basis of the regression of the offspring on their mothers h(2)(0P). These estimates were assessed for the concentration of PS, PSM and RAC in the wound response area of the seedlings and correspondingly in the heartwood of their mothers. The heritability was highest for the concentration of PS h(2)(0P). The findings of this study support the suggestion that the wounding of Scots pine seedlings may facilitate the development of an early testing method for breeding heartwood durability.

Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS): Evidence for Impairment and Heritability of Neurocognitive Functioning in Families of Schizophrenia Patients

PubMed Central

Calkins, Monica E.; Tepper, Ping; Gur, Ruben C.; Ragland, J. Daniel; Klei, Lambertus; Wiener, Howard W.; Richard, Jan; Savage, Robert M.; Allen, Trina B.; O'Jile, Judith; Devlin, Bernie; Kwentus, Joseph; Aliyu, Muktar H.; Bradford, L. DiAnne; Edwards, Neil; Lyons, Paul D.; Nimgaonkar, Vishwajit L.; Santos, Alberto B.; Go, Rodney C.P.; Gur, Raquel E.

2015-01-01

Objective Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. Method Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. Results The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/ flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. Conclusions Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies. PMID:20194479

Molecular Etiology of Hereditary Single-Side Deafness

PubMed Central

Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-01-01

Abstract Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD. The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes. Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS). We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form. PMID:26512583

Segregation analysis reveals evidence of a major gene for Alzheimer disease.

PubMed Central

Farrer, L A; Myers, R H; Connor, L; Cupples, L A; Growdon, J H

1991-01-01

In an attempt to resolve the relative influences of major genes, multifactorial heritability, and cohort effects on the susceptibility to Alzheimer disease (AD), complex segregation analysis was performed on 232 nuclear families. All families were consecutively ascertained through a single proband who was referred for diagnostic evaluation of a memory disorder. The results suggest that susceptibility to AD is determined, in part, by a major autosomal dominant allele with an additional multifactorial component. Single-locus, polygenic, sporadic, and no-transmission models, as well as recessive inheritance of the major effect, were significantly rejected. Excess transmission from the heterozygote was marginally significant and probably reflects the presence of phenocopies or perhaps the existence of two or more major loci for AD. The frequency of the AD susceptibility allele was estimated to be .038, but the major locus accounts for only 24% of the transmission variance, indicating a substantial role for other genetic and nongenetic mechanisms in the causation of AD. PMID:2035523

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

PubMed Central

Pineda, David A.; Lopera, Francisco; Puerta, Isabel C.; Trujillo-Orrego, Natalia; Aguirre-Acevedo, Daniel C.; Hincapié-Henao, Liliana; Arango, Clara P.; Acosta, Maria T.; Holzinger, Sandra I.; Palacio, Juan David; Pineda-Alvarez, Daniel E.; Velez, Jorge I.; Martinez, Ariel F.; Lewis, John E.

2014-01-01

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association. PMID:21779842

Genetic Variance in Homophobia: Evidence from Self- and Peer Reports.

PubMed

Zapko-Willmes, Alexandra; Kandler, Christian

2018-01-01

The present twin study combined self- and peer assessments of twins' general homophobia targeting gay men in order to replicate previous behavior genetic findings across different rater perspectives and to disentangle self-rater-specific variance from common variance in self- and peer-reported homophobia (i.e., rater-consistent variance). We hypothesized rater-consistent variance in homophobia to be attributable to genetic and nonshared environmental effects, and self-rater-specific variance to be partially accounted for by genetic influences. A sample of 869 twins and 1329 peer raters completed a seven item scale containing cognitive, affective, and discriminatory homophobic tendencies. After correction for age and sex differences, we found most of the genetic contributions (62%) and significant nonshared environmental contributions (16%) to individual differences in self-reports on homophobia to be also reflected in peer-reported homophobia. A significant genetic component, however, was self-report-specific (38%), suggesting that self-assessments alone produce inflated heritability estimates to some degree. Different explanations are discussed.

Genetic parameters for milk fatty acids in Danish Holstein cattle based on SNP markers using a Bayesian approach.

PubMed

Krag, Kristian; Poulsen, Nina A; Larsen, Mette K; Larsen, Lotte B; Janss, Luc L; Buitenhuis, Bart

2013-09-11

For several years, in human nutrition there has been a focus on the proportion of unsaturated fatty acids (UFA) and saturated fatty acids (SFA) found in bovine milk. The positive health-related properties of UFA versus SFA have increased the demand for food products with a higher proportion of UFA. To be able to change the UFA and SFA content of the milk by breeding it is important to know whether there is a genetic component underlying the individual FA in the milk. We have estimated the heritability for individual FA in the milk of Danish Holstein. For this purpose we used information of SNP markers instead of the traditional pedigree relationships. Estimates of heritability were moderate within the range of 0.10 for C18:1 trans-11 to 0.34 for C8:0 and C10:0, whereas the estimates for saturated fatty acids and unsaturated fatty acids were 0.14 and 0.18, respectively. Posterior standard deviations were in the range from 0.07 to 0.17. The correlation estimates showed a general pattern of two groups, one group mainly consisting of saturated fatty acids and one group mainly consisting of unsaturated fatty acids. The phenotypic correlation ranged from -0.95 (saturated fatty acids and unsaturated fatty acids) to 0.99 (unsaturated fatty acids and monounsaturated fatty acids) and the genomic correlation for fatty acids ranged from -0.29 to 0.91. The heritability estimates obtained in this study are in general accordance with heritability estimates from studies using pedigree data and/or a genomic relationship matrix in the context of a REML approach. SFA and UFA expressed a strong negative phenotypic correlation and a weaker genetic correlation. This is in accordance with the theory that SFA is synthesized de novo, while UFA can be regulated independently from the regulation of SFA by the feeding regime.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

PubMed Central

Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I; Scotland, Generation; Gottesman, R F; Griswold, M E; Gudnason, V; Harris, T B; Heiss, G; Hofman, A; Holliday, E G; Huffman, J; Kardia, S L R; Kochan, N; Knopman, D S; Kwok, J B; Lambert, J-C; Lee, T; Li, G; Li, S-C; Loitfelder, M; Lopez, O L; Lundervold, A J; Lundqvist, A; Mather, K A; Mirza, S S; Nyberg, L; Oostra, B A; Palotie, A; Papenberg, G; Pattie, A; Petrovic, K; Polasek, O; Psaty, B M; Redmond, P; Reppermund, S; Rotter, J I; Schmidt, H; Schuur, M; Schofield, P W; Scott, R J; Steen, V M; Stott, D J; van Swieten, J C; Taylor, K D; Trollor, J; Trompet, S; Uitterlinden, A G; Weinstein, G; Widen, E; Windham, B G; Jukema, J W; Wright, A F; Wright, M J; Yang, Q; Amieva, H; Attia, J R; Bennett, D A; Brodaty, H; de Craen, A J M; Hayward, C; Ikram, M A; Lindenberger, U; Nilsson, L-G; Porteous, D J; Räikkönen, K; Reinvang, I; Rudan, I; Sachdev, P S; Schmidt, R; Schofield, P R; Srikanth, V; Starr, J M; Turner, S T; Weir, D R; Wilson, J F; van Duijn, C; Launer, L; Fitzpatrick, A L; Seshadri, S; Mosley, T H; Deary, I J

2015-01-01

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. PMID:25644384

Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15.

PubMed

Madsen, Michael J; Knight, Stacey; Sweeney, Carol; Factor, Rachel; Salama, Mohamed; Stijleman, Inge J; Rajamanickam, Venkatesh; Welm, Bryan E; Arunachalam, Sasi; Jones, Brandt; Rachamadugu, Rakesh; Rowe, Kerry; Cessna, Melissa H; Thomas, Alun; Kushi, Lawrence H; Caan, Bette J; Bernard, Philip S; Camp, Nicola J

2018-06-01

Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding. Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis. Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors ( P = 2.6 × 10 -8 ). Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping. Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR . ©2018 American Association for Cancer Research.

Potential for adaptation to climate change in a coral reef fish.

PubMed

Munday, Philip L; Donelson, Jennifer M; Domingos, Jose A

2017-01-01

Predicting the impacts of climate change requires knowledge of the potential to adapt to rising temperatures, which is unknown for most species. Adaptive potential may be especially important in tropical species that have narrow thermal ranges and live close to their thermal optimum. We used the animal model to estimate heritability, genotype by environment interactions and nongenetic maternal components of phenotypic variation in fitness-related traits in the coral reef damselfish, Acanthochromis polyacanthus. Offspring of wild-caught breeding pairs were reared for two generations at current-day and two elevated temperature treatments (+1.5 and +3.0 °C) consistent with climate change projections. Length, weight, body condition and metabolic traits (resting and maximum metabolic rate and net aerobic scope) were measured at four stages of juvenile development. Additive genetic variation was low for length and weight at 0 and 15 days posthatching (dph), but increased significantly at 30 dph. By contrast, nongenetic maternal effects on length, weight and body condition were high at 0 and 15 dph and became weaker at 30 dph. Metabolic traits, including net aerobic scope, exhibited high heritability at 90 dph. Furthermore, significant genotype x environment interactions indicated potential for adaptation of maximum metabolic rate and net aerobic scope at higher temperatures. Net aerobic scope was negatively correlated with weight, indicating that any adaptation of metabolic traits at higher temperatures could be accompanied by a reduction in body size. Finally, estimated breeding values for metabolic traits in F2 offspring were significantly affected by the parental rearing environment. Breeding values at higher temperatures were highest for transgenerationally acclimated fish, suggesting a possible role for epigenetic mechanisms in adaptive responses of metabolic traits. These results indicate a high potential for adaptation of aerobic scope to higher temperatures, which could enable reef fish populations to maintain their performance as ocean temperatures rise. © 2016 John Wiley & Sons Ltd.

Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency.

PubMed

Tzvetkov, Mladen V; Matthaei, Johannes; Pojar, Sherin; Faltraco, Frank; Vogler, Sabrina; Prukop, Thomas; Seitz, Tina; Brockmöller, Jürgen

2018-05-01

Fenoterol is a widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter 1 (OCT1), a trait observed in 3% of Europeans and white Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity, and OCT1 inhibition in human hepatocytes reduced fenoterol uptake threefold. After administration of 180 µg of fenoterol to 39 healthy individuals, the OCT1-deficient individuals (zero active OCT1 alleles; n = 5) showed 1.9-fold greater systemic fenoterol exposure (P = 4.0 × 10 -5 ) and 1.7-fold lower volume of distribution (P = 8.0 × 10 -5 ). Correspondingly, the OCT1-deficient individuals had a 1.5-fold stronger increase in heart rate (P = 0.002), a 3.4-fold greater increase in blood glucose (P = 3.0 × 10 -5 ), and significantly lower serum potassium levels. In conclusion, heritable OCT1 deficiency significantly increases plasma concentrations of fenoterol and may be an important factor underlying the excess mortality associated with fenoterol. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

PubMed Central

Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede; Steel, Laura; Kobie, Julie; Abrams, Debra J.; Mentch, Frank D.; Glessner, Joseph T.; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Li, Dong; Maggadottir, S. Melkorka; Thomas, Kelly A.; Qui, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Flatø, Berit; Førre, Øystein; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L.; Latiano, Anna; Perez, Elena; Resnick, Elena; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Silverberg, Mark S.; Lie, Benedicte A.; Punaro, Marilynn; Russell, Richard K.; Wilson, David C.; Dubinsky, Marla C.; Monos, Dimitri S.; Annese, Vito; Munro, Jane E.; Wise, Carol; Chapel, Helen; Cunningham-Rundles, Charlotte; Orange, Jordan S.; Behrens, Edward M.; Sullivan, Kathleen E.; Kugathasan, Subra; Griffiths, Anne M.; Satsangi, Jack; Grant, Struan F. A.; Sleiman, Patrick M. A.; Finkel, Terri H.; Polychronakos, Constantin; Baldassano, Robert N.; Luning Prak, Eline T.; Ellis, Justine A.; Li, Hongzhe; Keating, Brendan J.; Hakonarson, Hakon

2015-01-01

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts. PMID:26450413

Heritabilities of measured and mid-infrared predicted milk fat globule size, milk fat and protein percentages, and their genetic correlations.

PubMed

Fleming, A; Schenkel, F S; Koeck, A; Malchiodi, F; Ali, R A; Corredig, M; Mallard, B; Sargolzaei, M; Miglior, F

2017-05-01

The objective of this study was to estimate the heritability of milk fat globule (MFG) size and mid-infrared (MIR) predicted MFG size in Holstein cattle. The genetic correlations between measured and predicted MFG size with milk fat and protein percentage were also investigated. Average MFG size was measured in 1,583 milk samples taken from 254 Holstein cows from 29 herds across Canada. Size was expressed as volume moment mean (D[4,3]) and surface moment mean (D[3,2]). Analyzed milk samples also had average MFG size predicted from their MIR spectral records. Fat and protein percentages were obtained for all test-day milk samples in the cow's lactation. Univariate and bivariate repeatability animal models were used to estimate heritability and genetic correlations. Moderate heritabilities of 0.364 and 0.466 were found for D[4,3] and D[3,2], respectively, and a strong genetic correlation was found between the 2 traits (0.98). The heritabilities for the MIR-predicted MFG size were lower than those estimated for the measured MFG size at 0.300 for predicted D[4,3] and 0.239 for predicted D[3,2]. The genetic correlation between measured and predicted D[4,3] was 0.685; the correlation was slightly higher between measured and predicted D[3,2] at 0.764, likely due to the better prediction accuracy of D[3,2]. Milk fat percentage had moderate genetic correlations with both D[4,3] and D[3,2] (0.538 and 0.681, respectively). The genetic correlation between predicted MFG size and fat percentage was much stronger (greater than 0.97 for both predicted D[4,3] and D[3,2]). The stronger correlation suggests a limitation for the use of the predicted values of MFG size as indicator traits for true average MFG size in milk in selection programs. Larger samples sizes are required to provide better evidence of the estimated genetic parameters. A genetic component appears to exist for the average MFG size in bovine milk, and the variation could be exploited in selection programs. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Child food neophobia is heritable, associated with less compliant eating, and moderates familial resemblance for BMI

PubMed Central

Faith, Myles S.; Heo, Moonseong; Keller, Kathleen L.; Pietrobelli, Angelo

2013-01-01

Objective The heritability of food neophobia, the tendency to avoid new foods, was tested in 4- to 7-year-old twins. We also examined whether food neophobia is associated with parent-child feeding relations or child body fat. Design and Methods We studied sixty-six same-sex twin pairs, including 37 monozygotic (MZ) and 29 dizygotic (DZ) pairs. Food neophobia was assessed by parent questionnaire (Child Food Neophobia Scale, CFNS), as were child feeding practices and “division of responsibility” feeding relations. Child anthropometry and percent body fat were directly measured. Results MZ and DZ twin pair correlations for food neophobia were r=0.71 and r= −0.01, respectively; heritability= 72%. Greater food neophobia was associated with reduced child eating compliance of prompted foods (p< 0.001) reduced eating compliance of initially refused foods (p< 0.001), and – among girls only – fewer parental food demands (p= 0.01). Interestingly, the correlation between maternal BMI and child BMI z-score was significant only for children high (p=0.03), but not low (p=0.55), in food neophobia. Conclusions Child food neophobia, a highly heritable trait previously linked to emotionality, was associated with less compliant parent-child feeding relations. Strategies to combat food neophobia and foster more harmonious feeding relationships may have a role in obesity prevention. PMID:23512929

Heritability of carotid intima-media thickness: a twin study.

PubMed

Zhao, Jinying; Cheema, Faiz A; Bremner, J Douglas; Goldberg, Jack; Su, Shaoyong; Snieder, Harold; Maisano, Carisa; Jones, Linda; Javed, Farhan; Murrah, Nancy; Le, Ngoc-Anh; Vaccarino, Viola

2008-04-01

To estimate the heritability of carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, independent of traditional coronary risk factors. We performed a classical twin study of carotid IMT using 98 middle-aged male twin pairs, 58 monozygotic (MZ) and 40 dizygotic (DZ) pairs, from the Vietnam Era Twin Registry. All twins were free of overt cardiovascular disease. Carotid IMT was measured by ultrasound. Bivariate and multivariate analyses were used to determine the association between traditional cardiovascular risk factors and carotid IMT. Intraclass correlation coefficients and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in carotid IMT. In our sample, the mean of the maximum carotid IMT was 0.75+/-0.11. Age, systolic blood pressure and HDL were significantly associated with carotid IMT. The intraclass correlation coefficient for carotid IMT was larger in MZ (0.66; 95% confidence interval [CI], 0.62-0.69) than in DZ twins (0.37; 95% CI, 0.29-0.44), and the unadjusted heritability was 0.69 (95% CI, 0.54-0.79). After adjusting for traditional coronary risk factors, the heritability of carotid IMT was slightly reduced but still of considerable magnitude (0.59; 95% CI, 0.39-0.73). Genetic factors have a substantial influence on the variation of carotid IMT. Most of this genetic effect occurs through pathways independent of traditional coronary risk factors.

Evolutionary potential of upper thermal tolerance: biogeographic patterns and expectations under climate change.

PubMed

Diamond, Sarah E

2017-02-01

How will organisms respond to climate change? The rapid changes in global climate are expected to impose strong directional selection on fitness-related traits. A major open question then is the potential for adaptive evolutionary change under these shifting climates. At the most basic level, evolutionary change requires the presence of heritable variation and natural selection. Because organismal tolerances of high temperature place an upper bound on responding to temperature change, there has been a surge of research effort on the evolutionary potential of upper thermal tolerance traits. Here, I review the available evidence on heritable variation in upper thermal tolerance traits, adopting a biogeographic perspective to understand how heritability of tolerance varies across space. Specifically, I use meta-analytical models to explore the relationship between upper thermal tolerance heritability and environmental variability in temperature. I also explore how variation in the methods used to obtain these thermal tolerance heritabilities influences the estimation of heritable variation in tolerance. I conclude by discussing the implications of a positive relationship between thermal tolerance heritability and environmental variability in temperature and how this might influence responses to future changes in climate. © 2016 New York Academy of Sciences.

The heritability of mental health and wellbeing defined using COMPAS-W, a new composite measure of wellbeing.

PubMed

Gatt, Justine M; Burton, Karen L O; Schofield, Peter R; Bryant, Richard A; Williams, Leanne M

2014-09-30

Mental health is not simply the absence of mental illness; rather it is a distinct entity representing wellness. Models of wellbeing have been proposed that emphasize components of subjective wellbeing, psychological wellbeing, or a combination of both. A new 26-item scale of wellbeing (COMPAS-W) was developed in a cohort of 1669 healthy adult twins (18-61 years). The scale was derived using factor analysis of multiple scales of complementary constructs and confirmed using tests of reliability and convergent validity. Bivariate genetic modeling confirmed its heritability. From an original 89 items we identified six independent subcomponents that contributed to wellbeing. The COMPAS-W scale and its subcomponents showed construct validity against psychological and physical health behaviors, high internal consistency (average r=0.71, Wellbeing r=0.84), and 12-month test-retest reliability (average r=0.62, Wellbeing r=0.82). There was a moderate contribution of genetics to total Wellbeing (heritability h(2)=48%) and its subcomponents: Composure (h(2)=24%), Own-worth (h(2)=42%), Mastery (h(2)=40%), Positivity (h(2)=42%), Achievement (h(2)=32%) and Satisfaction (h(2)=43%). Multivariate genetic modeling indicated genetic variance was correlated across the scales, suggesting common genetic factors contributed to Wellbeing and its subcomponents. The COMPAS-W scale provides a validated indicator of wellbeing and offers a new tool to quantify mental health. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The capture of heritable variation for genetic quality through social competition.

PubMed

Wolf, Jason B; Harris, W Edwin; Royle, Nick J

2008-09-01

In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.

Antisaccade performance in schizophrenia patients, their first-degree biological relatives, and community comparison subjects: data from the COGS study.

PubMed

Radant, Allen D; Dobie, Dorcas J; Calkins, Monica E; Olincy, Ann; Braff, David L; Cadenhead, Kristin S; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Meichle, Sean P; Millard, Steve P; Mintz, Jim; Nuechterlein, Keith H; Schork, Nicholas J; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Swerdlow, Neal R; Tsuang, Ming T; Turetsky, Bruce I; Tsuang, Debby W

2010-09-01

The antisaccade task is a widely used technique to measure failure of inhibition, an important cause of cognitive and clinical abnormalities found in schizophrenia. Although antisaccade performance, which reflects the ability to inhibit prepotent responses, is a putative schizophrenia endophenotype, researchers have not consistently reported the expected differences between first-degree relatives and comparison groups. Schizophrenia participants (n=219) from the large Consortium on the Genetics of Schizophrenia (COGS) sample (n=1078) demonstrated significant deficits on an overlap version of the antisaccade task compared to their first-degree relatives (n=443) and community comparison subjects (CCS; n=416). Although mean antisaccade performance of first-degree relatives was intermediate between schizophrenia participants and CCS, a linear mixed-effects model adjusting for group, site, age, and gender found no significant performance differences between the first-degree relatives and CCS. However, admixture analyses showed that two components best explained the distributions in all three groups, suggesting two distinct doses of an etiological factor. Given the significant heritability of antisaccade performance, the effects of a genetic polymorphism is one possible explanation of our results.

Genetic and Environmental Influences on Odor Identification Ability in the Very Old

PubMed Central

Doty, Richard L.; Petersen, Inge; Mensah, Nii; Christensen, Kaare

2013-01-01

Odor identification ability and cognition were measured in a population-based cohort of 1,222 very old twins and singletons, including 91 centenarians. Heritability for identifying odors was low, in contrast to that for cognition. Common genes were found to contribute to both olfaction and cognition. In a multiple regression model, sex, age, cognitive function, and smoking, but not APOEε4 status, were significant predictors of the olfactory test scores (all ps < 0.001). This study, along with data from other studies, suggests that indices of heritability for odor identification decline with age, likely reflecting adverse environmental influences on the smell system. PMID:21639645

Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle.

PubMed

Eaglen, Sophie A E; Coffey, Mike P; Woolliams, John A; Wall, Eileen

2012-07-28

The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle. Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (-maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models. On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (-maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (-maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence. For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (-maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions.

Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle

PubMed Central

2012-01-01

Background The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle. Methods Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (−maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models. Results and discussion On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (−maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (−maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence. Conclusions For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (−maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions. PMID:22839757

Robust LOD scores for variance component-based linkage analysis.

PubMed

Blangero, J; Williams, J T; Almasy, L

2000-01-01

The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

PubMed

Blokland, Gabriëlla A M; Mesholam-Gately, Raquelle I; Toulopoulou, Timothea; Del Re, Elisabetta C; Lam, Max; DeLisi, Lynn E; Donohoe, Gary; Walters, James T R; Seidman, Larry J; Petryshen, Tracey L

2017-07-01

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Estimation of genetic parameters for heat stress, including dominance gene effects, on milk yield in Thai Holstein dairy cattle.

PubMed

Boonkum, Wuttigrai; Duangjinda, Monchai

2015-03-01

Heat stress in tropical regions is a major cause that strongly negatively affects to milk production in dairy cattle. Genetic selection for dairy heat tolerance is powerful technique to improve genetic performance. Therefore, the current study aimed to estimate genetic parameters and investigate the threshold point of heat stress for milk yield. Data included 52 701 test-day milk yield records for the first parity from 6247 Thai Holstein dairy cattle, covering the period 1990 to 2007. The random regression test day model with EM-REML was used to estimate variance components, genetic parameters and milk production loss. A decline in milk production was found when temperature and humidity index (THI) exceeded a threshold of 74, also it was associated with the high percentage of Holstein genetics. All variance component estimates increased with THI. The estimate of heritability of test-day milk yield was 0.231. Dominance variance as a proportion to additive variance (0.035) indicated that non-additive effects might not be of concern for milk genetics studies in Thai Holstein cattle. Correlations between genetic and permanent environmental effects, for regular conditions and due to heat stress, were - 0.223 and - 0.521, respectively. The heritability and genetic correlations from this study show that simultaneous selection for milk production and heat tolerance is possible. © 2014 Japanese Society of Animal Science.

Evaluating the contribution of genetics and familial shared environment to common disease using the UK Biobank.

PubMed

Muñoz, María; Pong-Wong, Ricardo; Canela-Xandri, Oriol; Rawlik, Konrad; Haley, Chris S; Tenesa, Albert

2016-09-01

Genome-wide association studies have detected many loci underlying susceptibility to disease, but most of the genetic factors that contribute to disease susceptibility remain unknown. Here we provide evidence that part of the 'missing heritability' can be explained by an overestimation of heritability. We estimated the heritability of 12 complex human diseases using family history of disease in 1,555,906 individuals of white ancestry from the UK Biobank. Estimates using simple family-based statistical models were inflated on average by ∼47% when compared with those from structural equation modeling (SEM), which specifically accounted for shared familial environmental factors. In addition, heritabilities estimated using SNP data explained an average of 44.2% of the simple family-based estimates across diseases and an average of 57.3% of the SEM-estimated heritabilities, accounting for almost all of the SEM heritability for hypertension. Our results show that both genetics and familial environment make substantial contributions to familial clustering of disease.

Phylogenetic heritability of geographic range size in haematophagous ectoparasites: time of divergence and variation among continents.

PubMed

Krasnov, Boris R; Shenbrot, Georgy I; van der Mescht, Luther; Warburton, Elizabeth M; Khokhlova, Irina S

2018-04-12

To understand existence, patterns and mechanisms behind phylogenetic heritability in the geographic range size (GRS) of parasites, we measured phylogenetic signal (PS) in the sizes of both regional (within a region) and continental (within a continent) geographic ranges of fleas in five regions. We asked whether (a) GRS is phylogenetically heritable and (b) the manifestation of PS varies between regions. We also asked whether geographic variation in PS reflects the effects of the environment's spatiotemporal stability (e.g. glaciation disrupting geographic ranges) or is associated with time since divergence (accumulation differences among species over time). Support for the former hypothesis would be indicated by stronger PS in southern than in northern regions, whereas support for the latter hypothesis would be shown by stronger PS in regions with a large proportion of species belonging to the derived lineages than in regions with a large proportion of species belonging to the basal lineages. We detected significant PS in both regional and continental GRSs of fleas from Canada and in continental GRS of fleas from Mongolia. No PS was found in the GRS of fleas from Australia and Southern Africa. Venezuelan fleas demonstrated significant PS in regional GRS only. Local Indicators of Phylogenetic Association detected significant local positive autocorrelations of GRS in some clades even in regions in which PS has not been detected across the entire phylogeny. This was mainly characteristic of younger taxa.

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

PubMed Central

Benyamin, B; Pourcain, BSt; Davis, OS; Davies, G; Hansell, NK; Brion, M-JA; Kirkpatrick, RM; Cents, RAM; Franić, S; Miller, MB; Haworth, CMA; Meaburn, E; Price, TS; Evans, DM; Timpson, N; Kemp, J; Ring, S; McArdle, W; Medland, SE; Yang, J; Harris, SE; Liewald, DC; Scheet, P; Xiao, X; Hudziak, JJ; de Geus, EJC; Jaddoe, VWV; Starr, JM; Verhulst, FC; Pennell, C; Tiemeier, H; Iacono, WG; Palmer, LJ; Montgomery, GW; Martin, NG; Boomsma, DI; Posthuma, D; McGue, M; Wright, MJ; Smith, G Davey; Deary, IJ; Plomin, R; Visscher, PM

2014-01-01

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6–18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22–46% of phenotypic variation in childhood intelligence in the three largest cohorts (P = 3.9 × 10−15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P = 0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P = 6 × 10−5), 3.5% (P = 10−3) and 0.5% (P = 6 × 10−5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance. PMID:23358156

Low Cognitive Functioning in Nondemented 80+-Year-Old Twins Is Not Heritable.

ERIC Educational Resources Information Center

Petrill, Stephen A.; Johansson, Boo; Pedersen, Nancy L.; Berg, Stig; Plomin, Robert; Ahern, Frank; McClearn, Gerald E.

2001-01-01

Studied the genetic influence of low cognitive functioning in 200 pairs of twins aged at least 80 years and identified as not demented. Results suggest that the heritability of low cognitive functioning in this group was nonsignificant, but above-average cognitive functioning shows substantial group heritability. (SLD)

75 FR 46947 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

..., guidelines and programs for effectively reducing morbidity and mortality in newborns and children having or... Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting In accordance with... following meeting: Name: Secretary's Advisory Committee on Heritable Disorders in Newborns and Children...

Genetic and Phenotypic Parameter Estimates for Feed Intake and Other Traits in Growing Beef Cattle

USDA-ARS?s Scientific Manuscript database

Intake and feed efficiency were moderately heritable; however, residual feed intake was more heritable than intake and feed efficiency. Adjusting residual feed intake and feed efficiency for carcass fatness had little effect on heritability and correlations with remaining traits. Flight speed was ...

Heritability of antisocial behaviour at 9: do callous-unemotional traits matter?

PubMed

Viding, Essi; Jones, Alice P; Frick, Paul J; Moffitt, Terrie E; Plomin, Robert

2008-01-01

A previous finding from our group indicated that teacher-rated antisocial behaviour (AB) among 7-year-olds is particularly heritable in the presence of callous-unemotional (CU) traits. Using a sample of 1865 same-sex twin pairs, we employed DeFries-Fulker extremes analysis to investigate whether teacher-rated AB with/without CU traits also shows aetiological differences among 9-year-olds. Furthermore, we assessed whether the differences in the magnitude of heritability would be evident even when hyperactive symptoms were controlled for in the statistical analysis. AB among 9-year-olds was more heritable with than without concomitant CU. The heritability difference was even more pronounced in magnitude when hyperactive symptoms were controlled. CU traits thus appear to index one valid way of sub-typing children with early-onset AB.

The heritability of avoidant and dependent personality disorder assessed by personal interview and questionnaire.

PubMed

Gjerde, L C; Czajkowski, N; Røysamb, E; Orstavik, R E; Knudsen, G P; Ostby, K; Torgersen, S; Myers, J; Kendler, K S; Reichborn-Kjennerud, T

2012-12-01

Personality disorders (PDs) have been shown to be modestly heritable. Accurate heritability estimates are, however, dependent on reliable measurement methods, as measurement error deflates heritability. The aim of this study was to estimate the heritability of DSM-IV avoidant and dependent personality disorder, by including two measures of the PDs at two time points. Data were obtained from a population-based cohort of young adult Norwegian twins, of whom 8045 had completed a self-report questionnaire assessing PD traits. 2794 of these twins subsequently underwent a structured diagnostic interview for DSM-IV PDs. Questionnaire items predicting interview results were selected by multiple regression, and measurement models of the PDs were fitted in Mx. The heritabilities of the PD factors were 0.64 for avoidant PD and 0.66 for dependent PD. No evidence of common environment, that is, environmental factors that are shared between twins and make them similar, was found. Genetic and environmental contributions to avoidant and dependent PD seemed to be the same across sexes. The combination of both a questionnaire- and an interview assessment of avoidant and dependent PD results in substantially higher heritabilities than previously found using single-occasion interviews only. © 2012 John Wiley & Sons A/S.

Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.

PubMed

Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

2013-04-01

Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling.

Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.

PubMed

Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

2013-05-01

Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling.

Genome-wide association study identifies multiple loci influencing human serum metabolite levels

PubMed Central

Kettunen, Johannes; Tukiainen, Taru; Sarin, Antti-Pekka; Ortega-Alonso, Alfredo; Tikkanen, Emmi; Lyytikäinen, Leo-Pekka; Kangas, Antti J; Soininen, Pasi; Würtz, Peter; Silander, Kaisa; Dick, Danielle M; Rose, Richard J; Savolainen, Markku J; Viikari, Jorma; Kähönen, Mika; Lehtimäki, Terho; Pietiläinen, Kirsi H; Inouye, Michael; McCarthy, Mark I; Jula, Antti; Eriksson, Johan; Raitakari, Olli T; Salomaa, Veikko; Kaprio, Jaakko; Järvelin, Marjo-Riitta; Peltonen, Leena; Perola, Markus; Freimer, Nelson B; Ala-Korpela, Mika; Palotie, Aarno; Ripatti, Samuli

2013-01-01

Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10−10) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders. PMID:22286219

Serotonergic Genotypes, Neuroticism, and Financial Choices

PubMed Central

Kuhnen, Camelia M.; Samanez-Larkin, Gregory R.; Knutson, Brian

2013-01-01

Life financial outcomes carry a significant heritable component, but the mechanisms by which genes influence financial choices remain unclear. Focusing on a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR), we found that individuals possessing the short allele of this gene invested less in equities, were less engaged in actively making investment decisions, and had fewer credit lines. Short allele carriers also showed higher levels of the personality trait neuroticism, despite not differing from others with respect to cognitive skills, education, or wealth. Mediation analysis suggested that the presence of the 5-HTTLPR short allele decreased real life measures of financial risk taking through its influence on neuroticism. These findings show that 5-HTTLPR short allele carriers avoid risky and complex financial choices due to negative emotional reactions, and have implications for understanding and managing individual differences in financial choice. PMID:23382929

Childhood EEG frontal alpha power as a predictor of adolescent antisocial behavior: A twin heritability study

PubMed Central

Niv, Sharon; Ashrafulla, Syed; Tuvblad, Catherine; Joshi, Anand; Raine, Adrian; Leahy, Richard; Baker, Laura A.

2015-01-01

High EEG frontal alpha power (FAP) is thought to represent a state of low arousal in the brain, which has been related in past research to antisocial behavior (ASB). We investigated a longitudinal sample of 900 twins in two assessments in late childhood and mid-adolescence to verify whether relationships exist between FAP and both aggressive and nonaggressive ASB. ASB was measured by the Child Behavioral Checklist, and FAP was calculated using connectivity analysis methods that used principal components analysis to derive power of the most dominant frontal activation. Significant positive predictive relationships emerged in males between childhood FAP and adolescent aggressive ASB using multilevel mixed modeling. No concurrent relationships were found. Using bivariate biometric twin modeling analysis, the relationship between childhood FAP and adolescent aggressive ASB in males was found to be entirely due to genetic factors, which were correlated r = 0.22. PMID:25456277

Family environment, not heredity, accounts for family resemblances in food preferences and attitudes: a twin study.

PubMed

Rozin, P; Millman, L

1987-04-01

Monozygotic and same-sex dizygotic twin pairs reported on their food preferences, the variety of foods of the same general category (e.g. types of soup) in their diet, and their concern about contact of their food with disgusting or other unacceptable substances (contamination sensitivity). Although there was substantial resemblance between siblings for many of these items, there was no clear evidence for a heritable component on any item. The only case for which there was an interpretable and significantly greater resemblance among monozygotic than among dizygotic twins (out of 23 questions) was preferred degree of hotness resulting from chili pepper in foods. These results confirm the prediction that in omnivorous animals, such as humans, genetic predispositions will be minimal with respect to food. The modest sibling resemblances on a number of measures are primarily attributable to a shared environment.

Psychopathic Personality Traits and Environmental Contexts: Differential Correlates, Gender Differences, and Genetic Mediation

PubMed Central

Hicks, Brian M.; Carlson, Marie D.; Blonigen, Daniel M.; Patrick, Christopher J.; Iacono, William G.; MGue, Matt

2011-01-01

Theorists have speculated that primary psychopathy (or Factor 1 affective-interpersonal features) is prominently heritable whereas secondary psychopathy (or Factor 2 social deviance) is more environmentally determined. We tested this differential heritability hypothesis using a large adolescent twin sample. Trait-based proxies of primary and secondary psychopathic tendencies were assessed using Multidimensional Personality Questionnaire (MPQ; Tellegen & Waller, 2008) estimates of Fearless Dominance and Impulsive Antisociality, respectively (Benning et al., 2005). The environmental contexts of family, school, peers, and stressful life events were assessed using multiple raters and methods. Consistent with prior research, MPQ Impulsive Antisociality was robustly associated with each environmental risk factor, and these associations were significantly greater than those for MPQ Fearless Dominance. However, MPQ Fearless Dominance and Impulsive Antisociality exhibited similar heritability, and genetic effects mediated the associations between MPQ Impulsive Antisociality and the environmental measures. Results were largely consistent across male and female twins. We conclude that gene-environment correlations rather than main effects of genes and environments account for the differential environmental correlates of primary and secondary psychopathy. PMID:22452762

Fluctuating asymmetry and psychometric intelligence.

PubMed Central

Furlow, F B; Armijo-Prewitt, T; Gangestad, S W; Thornhill, R

1997-01-01

Little is known about the genetic nature of human psychometric intelligence (IQ), but it is widely assumed that IQ's heritability is at loci for intelligence per se. We present evidence consistent with a hypothesis that interindividual IQ differences are partly due to heritable vulnerabilities to environmental sources of developmental stress, an indirect genetic mechanism for the heritability of IQ. Using fluctuating asymmetry (FA) of the body (the asymmetry resulting from errors in the development of normally symmetrical bilateral traits under stressful conditions), we estimated the relative developmental instability of 112 undergraduates and administered to them Cattell's culture fair intelligence test (CFIT). A subsequent replication on 128 students was performed. In both samples, FA correlated negatively and significantly with CFIT scores. We propose two non-mutually exclusive physiological explanations for this correlation. First, external body FA may correlate negatively with the developmental integrity of the brain. Second, individual energy budget allocations and/or low metabolic efficiency in high-FA individuals may lower IQ scores. We review the data on IQ in light of our findings and conclude that improving developmental quality may increase average IQ in future generations. PMID:9265189

Heritable and Nonheritable Pathways to Early Callous-Unemotional Behaviors.

PubMed

Hyde, Luke W; Waller, Rebecca; Trentacosta, Christopher J; Shaw, Daniel S; Neiderhiser, Jenae M; Ganiban, Jody M; Reiss, David; Leve, Leslie D

2016-09-01

Callous-unemotional behaviors in early childhood signal higher risk for trajectories of antisocial behavior and callous-unemotional traits that culminate in later diagnoses of conduct disorder, antisocial personality disorder, and psychopathy. Studies demonstrate high heritability of callous-unemotional traits, but little research has examined specific heritable pathways to early callous-unemotional behaviors. Studies also indicate that positive parenting protects against the development of callous-unemotional traits, but genetically informed designs have not been used to confirm that these relationships are not the product of gene-environment correlations. In a sample of adopted children and their biological and adoptive mothers, the authors tested novel heritable and nonheritable pathways to preschool callous-unemotional behaviors. In an adoption cohort of 561 families, history of severe antisocial behavior assessed in biological mothers and observations of adoptive mother positive reinforcement at 18 months were examined as predictors of callous-unemotional behaviors at 27 months. Despite limited or no contact with offspring, biological mother antisocial behavior predicted early callous-unemotional behaviors. Adoptive mother positive reinforcement protected against early callous-unemotional behaviors. High levels of adoptive mother positive reinforcement buffered the effects of heritable risk for callous-unemotional behaviors posed by biological mother antisocial behavior. The findings elucidate heritable and nonheritable pathways to early callous-unemotional behaviors. The results provide a specific heritable pathway to callous-unemotional behaviors and compelling evidence that parenting is an important nonheritable factor in the development of callous-unemotional behaviors. The finding that positive reinforcement buffered heritable risk for callous-unemotional behaviors has important translational implications for the prevention of trajectories to serious antisocial behavior.

A meta-analysis of heritability of cognitive aging: minding the "missing heritability" gap.

PubMed

Reynolds, Chandra A; Finkel, Deborah

2015-03-01

The etiologies underlying variation in adult cognitive performance and cognitive aging have enjoyed much attention in the literature, but much of that attention has focused on broad factors, principally general cognitive ability. The current review provides meta-analyses of age trends in heritability of specific cognitive abilities and considers the profile of genetic and environmental factors contributing to cognitive aging to address the 'missing heritability' issue. Our findings, based upon evaluating 27 reports in the literature, indicate that verbal ability demonstrated declining heritability, after about age 60, as did spatial ability and perceptual speed more modestly. Trends for general memory, working memory, and spatial ability generally indicated stability, or small increases in heritability in mid-life. Equivocal results were found for executive function. A second meta-analysis then considered the gap between twin-based versus SNP-based heritability derived from population-based GWAS studies. Specifically, we considered twin correlation ratios to agnostically re-evaluate biometrical models across age and by cognitive domain. Results modestly suggest that nonadditive genetic variance may become increasingly important with age, especially for verbal ability. If so, this would support arguments that lower SNP-based heritability estimates result in part from uncaptured non-additive influences (e.g., dominance, gene-gene interactions), and possibly gene-environment (GE) correlations. Moreover, consistent with longitudinal twin studies of aging, as rearing environment becomes a distal factor, increasing genetic variance may result in part from nonadditive genetic influences or possible GE correlations. Sensitivity to life course dynamics is crucial to understanding etiological contributions to adult cognitive performance and cognitive aging.

Genetic and Environmental Effects on Weight, Height, and BMI Under 18 Years in a Chinese Population-Based Twin Sample.

PubMed

Liu, Qingqing; Yu, Canqing; Gao, Wenjing; Cao, Weihua; Lyu, Jun; Wang, Shengfeng; Pang, Zengchang; Cong, Liming; Dong, Zhong; Wu, Fan; Wang, Hua; Wu, Xianping; Jiang, Guohong; Wang, Binyou; Li, Liming

2015-10-01

This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex-limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0-2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15-17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59-87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences.

Three Approaches to Modeling Gene-Environment Interactions in Longitudinal Family Data: Gene-Smoking Interactions in Blood Pressure.

PubMed

Basson, Jacob; Sung, Yun Ju; de Las Fuentes, Lisa; Schwander, Karen L; Vazquez, Ana; Rao, Dabeeru C

2016-01-01

Blood pressure (BP) has been shown to be substantially heritable, yet identified genetic variants explain only a small fraction of the heritability. Gene-smoking interactions have detected novel BP loci in cross-sectional family data. Longitudinal family data are available and have additional promise to identify BP loci. However, this type of data presents unique analysis challenges. Although several methods for analyzing longitudinal family data are available, which method is the most appropriate and under what conditions has not been fully studied. Using data from three clinic visits from the Framingham Heart Study, we performed association analysis accounting for gene-smoking interactions in BP at 31,203 markers on chromosome 22. We evaluated three different modeling frameworks: generalized estimating equations (GEE), hierarchical linear modeling, and pedigree-based mixed modeling. The three models performed somewhat comparably, with multiple overlaps in the most strongly associated loci from each model. Loci with the greatest significance were more strongly supported in the longitudinal analyses than in any of the component single-visit analyses. The pedigree-based mixed model was more conservative, with less inflation in the variant main effect and greater deflation in the gene-smoking interactions. The GEE, but not the other two models, resulted in substantial inflation in the tail of the distribution when variants with minor allele frequency <1% were included in the analysis. The choice of analysis method should depend on the model and the structure and complexity of the familial and longitudinal data. © 2015 WILEY PERIODICALS, INC.

Use of weaning management group as a random effect for a more robust estimation of genetic parameters for post-weaning traits in Nellore cattle.

PubMed

Pedrosa, V B; Eler, J P; Ferraz, J B S; Groeneveld, E

2014-02-21

Data from 69,525 animals were used to compare two types of analyses, one of them having the weaning management group (WEMANG) included as an effect in the contemporary group (F_WEMANG) and the other considering the weaning management group as a random effect, not related to the mathematical model (R_WEMANG) for post-weaning traits. The components of (co)variance were estimated for pre-weaning traits (birth weight and weaning weight) and for post-weaning traits [scrotal circumference (SC), weight gain from weaning to 18 months of age (WG) and muscle score (MUSC)] in Nellore cattle, based on a complete animal model. Heritability of SC, WG and MUSC for the F_WEMANG model was equal to 0.46 ± 0.02, 0.38 ± 0.03 and 0.26 ± 0.01, and for the R_WEMANG model it was 0.45 ± 0.02, 0.31 ± 0.03 and 0.25 ± 0.01, respectively. Genetic correlations between all the studied traits varied between 0.07 ± 0.01 and 0.77 ± 0.03 in F_WEMANG and between 0.02 ± 0.01 and 0.76 ± 0.04 in R_WEMANG. The R_ WEMANG model allowed a decrease in the number of contemporary groups as well as an increase in the number of observations per group without significant alterations in heritability coefficients, for the post-weaning traits. Consequently, the analysis became more robust and avoided having contemporary groups with low variability.

Linear mixed model for heritability estimation that explicitly addresses environmental variation.

PubMed

Heckerman, David; Gurdasani, Deepti; Kadie, Carl; Pomilla, Cristina; Carstensen, Tommy; Martin, Hilary; Ekoru, Kenneth; Nsubuga, Rebecca N; Ssenyomo, Gerald; Kamali, Anatoli; Kaleebu, Pontiano; Widmer, Christian; Sandhu, Manjinder S

2016-07-05

The linear mixed model (LMM) is now routinely used to estimate heritability. Unfortunately, as we demonstrate, LMM estimates of heritability can be inflated when using a standard model. To help reduce this inflation, we used a more general LMM with two random effects-one based on genomic variants and one based on easily measured spatial location as a proxy for environmental effects. We investigated this approach with simulated data and with data from a Uganda cohort of 4,778 individuals for 34 phenotypes including anthropometric indices, blood factors, glycemic control, blood pressure, lipid tests, and liver function tests. For the genomic random effect, we used identity-by-descent estimates from accurately phased genome-wide data. For the environmental random effect, we constructed a covariance matrix based on a Gaussian radial basis function. Across the simulated and Ugandan data, narrow-sense heritability estimates were lower using the more general model. Thus, our approach addresses, in part, the issue of "missing heritability" in the sense that much of the heritability previously thought to be missing was fictional. Software is available at https://github.com/MicrosoftGenomics/FaST-LMM.

A proposed selection index for feedlot profitability based on estimated breeding values.

PubMed

van der Westhuizen, R R; van der Westhuizen, J

2009-04-22

It is generally accepted that feed intake and growth (gain) are the most important economic components when calculating profitability in a growth test or feedlot. We developed a single post-weaning growth (feedlot) index based on the economic values of different components. Variance components, heritabilities and genetic correlations for and between initial weight (IW), final weight (FW), feed intake (FI), and shoulder height (SHD) were estimated by multitrait restricted maximum likelihood procedures. The estimated breeding values (EBVs) and the economic values for IW, FW and FI were used in a selection index to estimate a post-weaning or feedlot profitability value. Heritabilities for IW, FW, FI, and SHD were 0.41, 0.40, 0.33, and 0.51, respectively. The highest genetic correlations were 0.78 (between IW and FW) and 0.70 (between FI and FW). EBVs were used in a selection index to calculate a single economical value for each animal. This economic value is an indication of the gross profitability value or the gross test value (GTV) of the animal in a post-weaning growth test. GTVs varied between -R192.17 and R231.38 with an average of R9.31 and a standard deviation of R39.96. The Pearson correlations between EBVs (for production and efficiency traits) and GTV ranged from -0.51 to 0.68. The lowest correlation (closest to zero) was 0.26 between the Kleiber ratio and GTV. Correlations of 0.68 and -0.51 were estimated between average daily gain and GTV and feed conversion ratio and GTV, respectively. These results showed that it is possible to select for GTV. The selection index can benefit feedlotting in selecting offspring of bulls with high GTVs to maximize profitability.

Heritability of specific language impairment depends on diagnostic criteria.

PubMed

Bishop, D V M; Hayiou-Thomas, M E

2008-04-01

Heritability estimates for specific language impairment (SLI) have been inconsistent. Four twin studies reported heritability of 0.5 or more, but a recent report from the Twins Early Development Study found negligible genetic influence in 4-year-olds. We considered whether the method of ascertainment influenced results and found substantially higher heritability if SLI was defined in terms of referral to speech and language pathology services than if defined by language test scores. Further analysis showed that presence of speech difficulties played a major role in determining whether a child had contact with services. Childhood language disorders that are identified by population screening are likely to have a different phenotype and different etiology from clinically referred cases. Genetic studies are more likely to find high heritability if they focus on cases who have speech difficulties and who have been referred for intervention.

Colour ornamentation in the blue tit: quantitative genetic (co)variances across sexes

PubMed Central

Charmantier, A; Wolak, M E; Grégoire, A; Fargevieille, A; Doutrelant, C

2017-01-01

Although secondary sexual traits are commonly more developed in males than females, in many animal species females also display elaborate ornaments or weaponry. Indirect selection on correlated traits in males and/or direct sexual or social selection in females are hypothesized to drive the evolution and maintenance of female ornaments. Yet, the relative roles of these evolutionary processes remain unidentified, because little is known about the genetic correlation that might exist between the ornaments of both sexes, and few estimates of sex-specific autosomal or sex-linked genetic variances are available. In this study, we used two wild blue tit populations with 9 years of measurements on two colour ornaments: one structurally based (blue crown) and one carotenoid based (yellow chest). We found significant autosomal heritability for the chromatic part of the structurally based colouration in both sexes, whereas carotenoid chroma was heritable only in males, and the achromatic part of both colour patches was mostly non heritable. Power limitations, which are probably common among most data sets collected so far in wild populations, prevented estimation of sex-linked genetic variance. Bivariate analyses revealed very strong cross-sex genetic correlations in all heritable traits, although the strength of these correlations was not related to the level of sexual dimorphism. In total, our results suggest that males and females share a majority of their genetic variation underlying colour ornamentation, and hence the evolution of these sex-specific traits may depend greatly on correlated responses to selection in the opposite sex. PMID:27577691

Analysis of morphological variability and heritability in the head of the Argentine Black and White Tegu (Salvator merianae): undisturbed vs. disturbed environments.

PubMed

Imhoff, Carolina; Giri, Federico; Siroski, Pablo; Amavet, Patricia

2018-04-01

The heterogeneity of biotic and abiotic factors influencing fitness produce selective pressures that promote local adaptation and divergence among different populations of the same species. In order for adaptations to be maintained through evolutionary time, heritable genetic variation controlling the expression of the morphological features under selection is necessary. Here we compare morphological shape variability and size of the cephalic region of Salvator merianae specimens from undisturbed environments to those of individuals from disturbed environments, and estimated heritability for shape and size using geometric morphometric and quantitative genetics tools. The results of these analyzes indicated that there are statistically significant differences in shape and size between populations from the two environments. Possibly, one of the main determinants of cephalic shape and size is adaptation to the characteristics of the environment and to the trophic niche. Individuals from disturbed environments have a cephalic region with less shape variation and also have a larger centroid size when compared to individuals from undisturbed environments. The high heritability values obtained for shape and size in dorsal view and right side view indicate that these phenotypic characters have a great capacity to respond to the selection pressures to which they are subjected. Data obtained here could be used as an important tool when establishing guidelines for plans for the sustainable use and conservation of S. merianae and other species living in disturbed areas. Copyright © 2018 Elsevier GmbH. All rights reserved.

An assessment of the reliability of quantitative genetics estimates in study systems with high rate of extra-pair reproduction and low recruitment.

PubMed

Bourret, A; Garant, D

2017-03-01

Quantitative genetics approaches, and particularly animal models, are widely used to assess the genetic (co)variance of key fitness related traits and infer adaptive potential of wild populations. Despite the importance of precision and accuracy of genetic variance estimates and their potential sensitivity to various ecological and population specific factors, their reliability is rarely tested explicitly. Here, we used simulations and empirical data collected from an 11-year study on tree swallow (Tachycineta bicolor), a species showing a high rate of extra-pair paternity and a low recruitment rate, to assess the importance of identity errors, structure and size of the pedigree on quantitative genetic estimates in our dataset. Our simulations revealed an important lack of precision in heritability and genetic-correlation estimates for most traits, a low power to detect significant effects and important identifiability problems. We also observed a large bias in heritability estimates when using the social pedigree instead of the genetic one (deflated heritabilities) or when not accounting for an important cause of resemblance among individuals (for example, permanent environment or brood effect) in model parameterizations for some traits (inflated heritabilities). We discuss the causes underlying the low reliability observed here and why they are also likely to occur in other study systems. Altogether, our results re-emphasize the difficulties of generalizing quantitative genetic estimates reliably from one study system to another and the importance of reporting simulation analyses to evaluate these important issues.

Heritability of Carotid Intima-Media Thickness: A Twin Study

PubMed Central

Zhao, Jinying; Cheema, Faiz A.; Bremner, J. Douglas; Goldberg, Jack; Su, Shaoyong; Snieder, Harold; Maisano, Carisa; Jones, Linda; Javed, Farhan; Murrah, Nancy; Le, Ngoc-Anh; Vaccarino, Viola

2008-01-01

Objective To estimate the heritability of carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, independent of traditional coronary risk factors. Methods and Results We performed a classical twin study of carotid IMT using 98 middle-aged male twin pairs, 58 monozygotic (MZ) and 40 dizygotic (DZ) pairs, from the Vietnam Era Twin Registry. All twins were free of overt cardiovascular disease. Carotid IMT was measured by ultrasound. Bivariate and multivariate analyses were used to determine the association between traditional cardiovascular risk factors and carotid IMT. Intraclass correlation coefficients and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in carotid IMT. In our sample, the mean of the maximum carotid IMT was 0.75 ± 0.11. Age, systolic blood pressure and HDL were significantly associated with carotid IMT. The intraclass correlation coefficient for carotid IMT was larger in MZ (0.66; 95% confidence interval [CI], 0.62–0.69) than in DZ twins (0.37; 95% CI, 0.29–0.44), and the unadjusted heritability was 0.69 (95% CI, 0.54–0.79). After adjusting for traditional coronary risk factors, the heritability of carotid IMT was slightly reduced but still of considerable magnitude (0.59; 95% CI, 0.39–0.73). Conclusion Genetic factors have a substantial influence on the variation of carotid IMT. Most of this genetic effect occurs through pathways independent of traditional coronary risk factors. PMID:17825306

Cross-Study Differences in the Etiology of Reading Comprehension: a Meta-Analytical Review of Twin Studies.

PubMed

Little, Callie W; Haughbrook, Rasheda; Hart, Sara A

2017-01-01

Numerous twin studies have examined the genetic and environmental etiology of reading comprehension, though it is likely that etiological estimates are influenced by unidentified sample conditions (e.g. Tucker-Drob and Bates, Psychol Sci:0956797615612727, 2015). The purpose of this meta-analysis was to average the etiological influences of reading comprehension and to explore the potential moderators influencing these estimates. Results revealed an average heritability estimate of h 2  = 0.59, with significant variation in estimates across studies, suggesting potential moderation. Moderation results indicated publication year, grade level, project, zygosity methods, and response type moderated heritability estimates. The average shared environmental estimate was c 2  = 0.16, with publication year, grade and zygosity methods acting as significant moderators. These findings support the role of genetics on reading comprehension, and a small significant role of shared environmental influences. The results suggest that our interpretation of how genes and environments influence reading comprehension should reflect aspects of study and sample.

Disproportionate Contributions of Select Genomic Compartments and Cell Types to Genetic Risk for Coronary Artery Disease

PubMed Central

Won, Hong-Hee; Natarajan, Pradeep; Dobbyn, Amanda; Jordan, Daniel M.; Roussos, Panos; Lage, Kasper; Raychaudhuri, Soumya

2015-01-01

Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function. First, we examined the heritability of MI/CAD according to genomic compartments. We observed that single nucleotide polymorphisms (SNPs) residing within nearby regulatory regions show significant polygenicity and contribute between 59–71% of the heritability for MI/CAD. Second, we showed that the polygenicity and heritability explained by these SNPs are enriched in histone modification marks in specific cell types. Third, we found that a statistically higher number of 45 MI/CAD-associated SNPs that have been identified from large-scale GWAS studies reside within certain functional elements of the genome, particularly in active enhancer and promoter regions. Finally, we observed significant heterogeneity of this signal across cell types, with strong signals observed within adipose nuclei, as well as brain and spleen cell types. These results suggest that the genetic etiology of MI/CAD is largely explained by tissue-specific regulatory perturbation within the human genome. PMID:26509271

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence

PubMed Central

Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Smith, G D; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

2016-01-01

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case–control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence. PMID:26239293

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

PubMed

Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Davey Smith, G; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

2016-08-01

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

Genetic determination of adiponectin and its relationship with body fat topography in multigenerational families of African heritage.

PubMed

Miljkovic-Gacic, Iva; Wang, Xiaojing; Kammerer, Candace M; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Kuller, Lewis H; Evans, Rhobert W; Zmuda, Joseph M

2007-02-01

Adiponectin, an adipose-specific protein, is negatively associated with adiposity, insulin sensitivity, and diabetes. Very few studies have examined the role of heredity in the regulation of adiponectin and its association with body fat among individuals of African heritage. Thus, we measured fasting serum adiponectin levels by radioimmunoassay and body composition by dual-energy x-ray absorptiometry (DEXA) in 402 individuals aged 18 to 103 years belonging to 7 multigenerational families of African heritage in the relatively homogeneous island population of Tobago. Heritability of adiponectin was 33.2% (P < .01), and age, sex, and body mass index explained 23.4% of the variance in adiponectin. Sex-specific heritability was significant in men (heritability, 34%; P < .05), but not in women. The inverse associations between body mass index and percentage of body fat and adiponectin, independent of age and height, were much stronger in women (all P values <.001) than in men. However, percentage of trunk fat was consistently strongly associated with adiponectin in both men (r = -0.40, P < .001) and women (r = -0.44, P < .001), independent of age and height. This study suggests that genetic factors are a significant source of interindividual differences in circulating adiponectin among Afro-Caribbeans. Adiponectin may serve as a promising quantitative intermediate trait in studies designed to map the genes underlying diabetes and obesity in this population.

The contribution of additive genetic variation to personality variation: heritability of personality.

PubMed

Dochtermann, Ned A; Schwab, Tori; Sih, Andrew

2015-01-07

Individual animals frequently exhibit repeatable differences from other members of their population, differences now commonly referred to as 'animal personality'. Personality differences can arise, for example, from differences in permanent environmental effects--including parental and epigenetic contributors--and the effect of additive genetic variation. Although several studies have evaluated the heritability of behaviour, less is known about general patterns of heritability and additive genetic variation in animal personality. As overall variation in behaviour includes both the among-individual differences that reflect different personalities and temporary environmental effects, it is possible for personality to be largely genetically influenced even when heritability of behaviour per se is quite low. The relative contribution of additive genetic variation to personality variation can be estimated whenever both repeatability and heritability are estimated for the same data. Using published estimates to address this issue, we found that approximately 52% of animal personality variation was attributable to additive genetic variation. Thus, while the heritability of behaviour is often moderate or low, the heritability of personality is much higher. Our results therefore (i) demonstrate that genetic differences are likely to be a major contributor to variation in animal personality and (ii) support the phenotypic gambit: that evolutionary inferences drawn from repeatability estimates may often be justified. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Genetic and Environmental Influences on Testosterone in Adolescents: Evidence for Sex Differences

PubMed Central

Harden, K. Paige; Kretsch, Natalie; Tackett, Jennifer L.; Tucker-Drob, Elliot M.

2015-01-01

The current study investigated the genetic and environmental etiology of individual differences in salivary testosterone during adolescence, using data from 49 pairs of monozygotic twins and 68 pairs of dizygotic twins, ages 14–19 years (M = 16.0 years). Analyses tested for sex differences in genetic and environmental influences on testosterone and its relation to pubertal development. Among adolescent males, individual differences in testosterone were substantially heritable (55%), and significantly associated with self-reported pubertal status (controlling for age) via common genetic influences. In contrast, there was no heritable variation in testosterone for females, and testosterone in females was not significantly associated with pubertal status after controlling for age. Rather, environmental influences shared by twins raised together accounted for all of the familial similarity in female testosterone (53%). This study adds to a small but growing body of research that investigates genetic influences on individual differences in behaviorally-relevant hormones. PMID:24523135

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence.

PubMed

Zavos, Helena M S; Freeman, Daniel; Haworth, Claire M A; McGuire, Philip; Plomin, Robert; Cardno, Alastair G; Ronald, Angelica

2014-09-01

The onset of psychosis is usually preceded by psychotic experiences (PE). Little is known about the etiology of PE and whether the degree of genetic and environmental influences varies across different levels of severity. A recognized challenge is to identify individuals at high risk of developing psychotic disorders prior to disease onset. To investigate the degree of genetic and environmental influences on specific PE, assessed dimensionally, in adolescents in the community and in those who have many, frequent experiences (defined using quantitative cutoffs). We also assessed the degree of overlap in etiological influences between specific PE. Structural equation model-fitting, including univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis, and the Cherny method, was used to analyze a representative community sample of 5059 adolescent twin pairs (mean [SD] age, 16.31 [0.68] years) from England and Wales. Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia, as well as parent-rated negative symptoms). Genetic influences were apparent for all PE (15%-59%), with modest shared environment for hallucinations and negative symptoms (17%-24%) and significant nonshared environment (49%-64%) for the self-rated scales and 17% for parent-rated negative symptoms. Three empirical approaches converged to suggest that the etiology in extreme-scoring groups (most extreme scoring: 5%, 10%, and 15%) did not differ significantly from that of the whole distribution. There was no linear change in heritability across the distribution of PE, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the PE that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities, 0.54-0.71). These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent PE and milder, less frequent manifestations in adolescents. Individual PE in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of PE, being highest for paranoia and parent-rated negative symptoms and lowest for hallucinations.

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: A twin study of specific psychotic experiences in adolescence

PubMed Central

Zavos, Helena M.S.; Freeman, Daniel; Haworth, Claire M. A.; McGuire, Philip; Plomin, Robert; Cardno, Alastair G.; Ronald, Angelica

2014-01-01

Context The onset of psychosis is usually preceded by psychotic experiences, but little is known about their causes. The present study investigated the degree of genetic and environmental influences on specific psychotic experiences, assessed dimensionally, in adolescence in the community and in individuals with many, frequent experiences (defined using quantitative cut-offs). The degree of overlap in etiological influences between specific psychotic experiences was also investigated Objective Investigate degree of genetic and environmental influences on specific psychotic experiences, assessed dimensionally, in adolescence in the community and in individuals having many, frequent experiences (defined using quantitative cut-offs). Test degree of overlap in etiological influences between specific psychotic experiences. Design Classic twin design. Structural equation model-fitting. Univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis and the Cherny Method. Setting Representative community sample of twins from England and Wales. Participants 5059 adolescent twin pairs (Mean age: 16.31 yrs, SD: 0.68 yrs). Main outcome measure Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia; parent-rated negative symptoms). Results Genetic influences were apparent for all psychotic experiences (15-59%) with modest shared environment for hallucinations and negative symptoms (17-24%) and significant nonshared environment (49-64% for the self-rated scales, 17% for Parent-rated Negative Symptoms). Three different empirical approaches converged to suggest that the etiology in extreme groups (most extreme-scoring 5%, 10% and 15%) did not differ significantly from that of the whole distribution. There was no linear change in the heritability across the distribution of psychotic experiences, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the psychotic experiences that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities = .54-.71). Conclusions and Relevance These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent psychotic experiences and milder, less frequent manifestations in adolescents. Individual psychotic experiences in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of psychotic experience, being highest for paranoia and parent-rated negative symptoms, and lowest for hallucinations. PMID:25075799

Intrafamilial aggregation and heritability of tissue Doppler indexes of left ventricular diastolic function in a group of African descent.

PubMed

Peterson, Vernice R; Norton, Gavin R; Libhaber, Carlos D; Maseko, Muzi J; Sareli, Pinhas; Woodiwiss, Angela J

2016-06-01

Although several indexes of left ventricular (LV) diastolic function show heritability, the genetic influence on the tissue Doppler index, E/e' (early transmitral velocity/velocity of myocardial tissue lengthening), an index of LV filling pressures in those of black African descent is currently unknown. Furthermore, whether any genetic influences on E/e' are through an impact of LV remodeling or aortic function is unknown. Intrafamilial aggregation and heritability (SAGE software) of E/e' (echocardiography) were assessed in 129 nuclear families (29 spouse pairs, 216 parent-child pairs, and 113 sibling-sibling pairs) from an urban developing community of black Africans, independent of LV mass index (LVMI), LV relative wall thickness (RWT), central aortic systolic pressure (SBPc), and backward wave pressures (Pb) (applanation tonometry, SphygmoCor software). Independent of confounders including LVMI and RWT, E/e' was correlated in parent-child (r = 0.23; P < .001) and sibling-sibling (r = 0.29; P < .005), but not in spouse (r = 0.13; P = .51) pairs. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.29; P < .005) pairs persisted with adjustments for SBPc. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.26; P < .01) pairs also persisted with adjustments for Pb. Independent of confounders including LVMI and RWT, E/e' showed significant heritability (h(2) ± standard error of the mean [SEM] = 0.51 ± 0.11; P < .0001) which similarly persisted with adjustments for SBPc (h(2) ± SEM = 0.50 ± 0.11; P < .0001) and Pb (h(2) ± SEM = 0.49 ± 0.11; P < .0001). In conclusion, in a group of African ancestry, independent of LV remodeling and aortic function, E/e' shows significant intrafamilial aggregation and robust heritability. Hence, genetic factors may play an important role in determining moderate-to-severe LV diastolic dysfunction independent of cardiac remodeling or aortic function in groups of black African ancestry. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Genetic effects on refraction and correlation with hemodynamic variables: a twin study.

PubMed

Toth, G Zs; Tarnoki, Adam Domonkos; Tarnoki, D L; Racz, A; Szekelyhidi, Z; Littvay, L; Karlinger, K; Lannert, A; Molnar, A A; Garami, Zs; Berczi, V; Suveges, I; Nemeth, J

2014-09-01

Spherical equivalent (SE) has not been linked to increased cardiovascular morbidity. Methods: 132 Hungarian twins(age 43.3±16.9 years) underwent refraction measurements (Huvitz MRK-3100 Premium AutoRefractokeratometer)and oscillometry (TensioMed Arteriograph). Results: Heritability analysis indicated major role for genetic components in the presence of right and left SE (82.7%, 95%CI, 62.9 to 93.7%, and 89.3%, 95%CI, 72.8 to 96.6%),while unshared environmental effects accounted for 17% (95%CI, 6.3% to 37%), and 11% (95%CI, 3.4% to 26.7%)of variations adjusted for age and sex. Bilateral SE showed weak age-dependent correlations with augmentation index (AIx), aortic pulse wave velocity (r ranging between 0.218 and 0.389, all p < 0.01), aortic systolic blood pressure and pulse pressure (r between 0.188 and 0.289, p < 0.05). Conclusions: These findings support heritability of spherical equivalent, which does not coexist with altered hemodynamics (e.g. accelerated arterial aging).Accordingly, SE and the investigated hemodynamic parameters seem neither phenotypically nor genetically associated.

Heritability and genetic correlations for volume, foxtails, and other characteristics of Caribbean pine in Puerto Rico

Treesearch

F. Thomas Ledig; J.L. Whitmore

1981-01-01

Caribbean pine is an important exotic being bred throughout the tropics, but published estimates are lacking for heritability of economically important traits and the genetic correlations between them. Based on a Puerto Rican trial of 16 open-pollinated parents of var. hondurensis selected in Belize, heritabilities for a number of characteristics...

77 FR 47857 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting In accordance with... Disorders in Newborns and Children. Dates and Times: September 13, 2012, 8:30 a.m. to 6:00 p.m., September... Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC), as authorized by Public Law...

Heritable DNA methylation in CD4+ cells among complex families displays genetic and non-genetic effects

USDA-ARS?s Scientific Manuscript database

DNA methylation at CpG sites is both heritable and influenced by environment, but the relative contributions of each to DNA methylation levels are unclear. We conducted a heritability analysis of CpG methylation in human CD4+ cells across 975 individuals from 163 families in the Genetics of Lipid-lo...

Genetic parameters of cheese yield and curd nutrient recovery or whey loss traits predicted using Fourier-transform infrared spectroscopy of samples collected during milk recording on Holstein, Brown Swiss, and Simmental dairy cows.

PubMed

Cecchinato, A; Albera, A; Cipolat-Gotet, C; Ferragina, A; Bittante, G

2015-07-01

Cheese yield is the most important technological parameter in the dairy industry in many countries. The aim of this study was to infer (co)variance components for cheese yields (CY) and nutrient recoveries in curd (REC) predicted using Fourier-transform infrared (FTIR) spectroscopy of samples collected during milk recording on Holstein, Brown Swiss, and Simmental dairy cows. A total of 311,354 FTIR spectra representing the test-day records of 29,208 dairy cows (Holstein, Brown Swiss, and Simmental) from 654 herds, collected over a 3-yr period, were available for the study. The traits of interest for each cow consisted of 3 cheese yield traits (%CY: fresh curd, curd total solids, and curd water as a percent of the weight of the processed milk), 4 curd nutrient recovery traits (REC: fat, protein, total solids, and the energy of the curd as a percent of the same nutrient in the processed milk), and 3 daily cheese production traits (daily fresh curd, total solids, and the water of the curd per cow). Calibration equations (freely available upon request to the corresponding author) were used to predict individual test-day observations for these traits. The (co)variance components were estimated for the CY, REC, milk production, and milk composition traits via a set of 4-trait analyses within each breed. All analyses were performed using REML and linear animal models. The heritabilities of the %CY were always higher for Holstein and Brown Swiss cows (0.22 to 0.33) compared with Simmental cows (0.14 to 0.18). In general, the fresh cheese yield (%CYCURD) showed genetic variation and heritability estimates that were slightly higher than those of its components, %CYSOLIDS and %CYWATER. The parameter RECPROTEIN was the most heritable trait in all the 3 breeds, with values ranging from 0.32 to 0.41. Our estimation of the genetic relationships of the CY and REC with milk production and composition revealed that the current selection strategies used in dairy cattle are expected to exert only limited effects on the REC traits. Instead, breeders may be able to exploit genetic variations in the %CY, particularly RECFAT and RECPROTEIN. This last component is not explained by the milk protein content, suggesting that its direct selection could be beneficial for cheese production aptitude. Collectively, our findings indicate that breeding strategies aimed at enhancing CY and REC could be easily and rapidly implemented for dairy cattle populations in which FTIR spectra are routinely acquired from individual milk samples. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots.

PubMed

Balyejusa Kizito, Elizabeth; Rönnberg-Wästljung, Ann-Christin; Egwang, Thomas; Gullberg, Urban; Fregene, Martin; Westerbergh, Anna

2007-09-01

Cassava (Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S(1) population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad-sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava.

Familial concordance for age at natural menopause: results from the Breakthrough Generations Study.

PubMed

Morris, Danielle H; Jones, Michael E; Schoemaker, Minouk J; Ashworth, Alan; Swerdlow, Anthony J

2011-09-01

Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance. Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models. Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P < 0.001) or non-twin sister (odds ratio, 5.5; P < 0.001) had had an early menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P < 0.01; non-twin sister: odds ratio, 2.3; P < 0.001). Estimated heritability was 41.6% (P < 0.01), with an additional 13.6% (P = 0.02) of the variation in menopause age attributed to environmental factors shared by sisters. We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.

A Veritable Menagerie of Heritable Bacteria from Ants, Butterflies, and Beyond: Broad Molecular Surveys and a Systematic Review

PubMed Central

Russell, Jacob A.; Funaro, Colin F.; Giraldo, Ysabel M.; Goldman-Huertas, Benjamin; Suh, David; Kronauer, Daniel J. C.; Moreau, Corrie S.; Pierce, Naomi E.

2012-01-01

Maternally transmitted bacteria have been important players in the evolution of insects and other arthropods, affecting their nutrition, defense, development, and reproduction. Wolbachia are the best studied among these and typically the most prevalent. While several other bacteria have independently evolved a heritable lifestyle, less is known about their host ranges. Moreover, most groups of insects have not had their heritable microflora systematically surveyed across a broad range of their taxonomic diversity. To help remedy these shortcomings we used diagnostic PCR to screen for five groups of heritable symbionts—Arsenophonus spp., Cardinium hertigii, Hamiltonella defensa, Spiroplasma spp., and Wolbachia spp.—across the ants and lepidopterans (focusing, in the latter case, on two butterfly families—the Lycaenidae and Nymphalidae). We did not detect Cardinium or Hamiltonella in any host. Wolbachia were the most widespread, while Spiroplasma (ants and lepidopterans) and Arsenophonus (ants only) were present at low levels. Co-infections with different Wolbachia strains appeared especially common in ants and less so in lepidopterans. While no additional facultative heritable symbionts were found among ants using universal bacterial primers, microbes related to heritable enteric bacteria were detected in several hosts. In summary, our findings show that Wolbachia are the dominant heritable symbionts of ants and at least some lepidopterans. However, a systematic review of symbiont frequencies across host taxa revealed that this is not always the case across other arthropods. Furthermore, comparisons of symbiont frequencies revealed that the prevalence of Wolbachia and other heritable symbionts varies substantially across lower-level arthropod taxa. We discuss the correlates, potential causes, and implications of these patterns, providing hypotheses on host attributes that may shape the distributions of these influential bacteria. PMID:23284655

On the nature and nurture of intelligence and specific cognitive abilities: the more heritable, the more culture dependent.

PubMed

Kan, Kees-Jan; Wicherts, Jelte M; Dolan, Conor V; van der Maas, Han L J

2013-12-01

To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to demonstrate greater heritability coefficients than do culture-reduced subtests; and (b) in samples of both adults and children, a subtest's proportion of variance shared with general intelligence is a function of its cultural load. These findings require an explanation because they do not follow from mainstream theories of intelligence. The findings are consistent with our hypothesis that heritability coefficients differ across cognitive abilities as a result of differences in the contribution of genotype-environment covariance. The counterintuitive finding that the most heritable abilities are the most culture-dependent abilities sheds a new light on the long-standing nature-nurture debate of intelligence.

Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

2010-01-01

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

Cross-study differences in the etiology of reading comprehension: A meta-analytical review of twin studies

PubMed Central

Little, Callie W; Haughbrook, Rasheda; Hart, Sara A

2016-01-01

Numerous twin studies have been published examining the genetic and environmental etiology of reading comprehension, though the etiological estimates may be influenced currently unidentified sample conditions (e.g., Tucker-Drob & Bates, 2015). The purpose of the current meta-analysis was to average the etiological influences of reading comprehension and to explore the potential moderators that may be influencing these estimates. Results revealed an average heritability estimate of h2 = .59, with significant variation in estimates across studies, suggesting potential moderation. Heritability was moderated by publication year, grade level, project, zygosity determination method, and response type. The average shared environmental estimate was c2 = .16, with publication year, grade and zygosity determination method acting as significant moderators. These findings support the large role of genetic influences on reading comprehension, and a small but significant role of shared environmental influences. The significant moderators of etiological influences within the current synthesis suggest our interpretation of how genes and environment influence reading comprehension should reflect aspects of study and sample. PMID:27630039

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

PubMed

Cadby, Gemma; Melton, Phillip E; McCarthy, Nina S; Almeida, Marcio; Williams-Blangero, Sarah; Curran, Joanne E; VandeBerg, John L; Hui, Jennie; Beilby, John; Musk, A W; James, Alan L; Hung, Joseph; Blangero, John; Moses, Eric K

2018-01-01

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yauk, C.L.; Quinn, J.S.

The authors used multi-locus DNA fingerprinting to examine families of herring gulls (Larus argentatus) from a genotoxically contaminated site (Hamilton Harbour) and from a pristine location (Kent Island, Bay of Fundy) to show significant differences in mutation rates between the locations. Overall the authors identified 17 mutant bands from 15 individuals of the 35 examined from Hamilton Harbour, and 7 mutant fragments from 7 individuals, of the 43 examined from Kent Island; a mutation frequency of 0.429 per nestling for Hamilton Harbour and 0.163 for Kent Island. The total number of individuals with mutant bands was significantly higher at Hamiltonmore » Harbour than at Kent Island (X{sup 2}=6.734; df = 1; P < 0.01). Ongoing analysis of other less contaminated sites also reveals lower mutation rates than those seen in Hamilton Harbour. With multi-locus DNA fingerprinting many regions of the genome can be surveyed simultaneously. The tandemly repeated arrays of nucleotides examined with DNA fingerprinting are known to have elevated rates of mutation. Furthermore, the mutations seen with DNA fingerprinting are predominantly heritable. Other biomarkers currently used in situ are not able to monitor direct and heritable DNA mutation, or measure biological endpoints that frequently result in spontaneous abortion creating difficulty in observing significantly elevated levels in viable offspring. The authors suggest that multilocus DNA fingerprinting can be used as a biomarker to identify potentially heritable risks before the onset of other types of ecological damage. This approach provides a direct measure of mutation in situ and in vivo in a vertebrate species under ambient conditions.« less

Determinants of day-night difference in blood pressure, a comparison with determinants of daytime and night-time blood pressure.

PubMed

Musameh, M D; Nelson, C P; Gracey, J; Tobin, M; Tomaszewski, M; Samani, N J

2017-01-01

Blunted day-night difference in blood pressure (BP) is an independent cardiovascular risk factor, although there is limited information on determinants of diurnal variation in BP. We investigated determinants of day-night difference in systolic (SBP) and diastolic (DBP) BP and how these compared with determinants of daytime and night-time SBP and DBP. We analysed the association of mean daytime, mean night-time and mean day-night difference (defined as (mean daytime-mean night-time)/mean daytime) in SBP and DBP with clinical, lifestyle and biochemical parameters from 1562 adult individuals (mean age 38.6) from 509 nuclear families recruited in the GRAPHIC Study. We estimated the heritability of the various BP phenotypes. In multivariate analysis, there were significant associations of age, sex, markers of adiposity (body mass index and waist-hip ratio), plasma lipids (total and low-density lipoprotein cholesterol and triglycerides), serum uric acid, alcohol intake and current smoking status on daytime or night-time SBP and/or DBP. Of these, only age (P=4.7 × 10 -5 ), total cholesterol (P=0.002), plasma triglycerides (P=0.006) and current smoking (P=3.8 × 10 -9 ) associated with day-night difference in SBP, and age (P=0.001), plasma triglyceride (P=2.2 × 10 -5 ) and current smoking (3.8 × 10 -4 ) associated with day-night difference in DBP. 24-h, daytime and night-time SBP and DBP showed substantial heritability (ranging from 18-43%). In contrast day-night difference in SBP showed a lower heritability (13%) while heritability of day-night difference in DBP was not significant. These data suggest that specific clinical, lifestyle and biochemical factors contribute to inter-individual variation in daytime, night-time and day-night differences in SBP and DBP. Variation in day-night differences in BP is largely non-genetic.

Determinants of day–night difference in blood pressure, a comparison with determinants of daytime and night-time blood pressure

PubMed Central

Musameh, M D; Nelson, C P; Gracey, J; Tobin, M; Tomaszewski, M; Samani, N J

2017-01-01

Blunted day–night difference in blood pressure (BP) is an independent cardiovascular risk factor, although there is limited information on determinants of diurnal variation in BP. We investigated determinants of day–night difference in systolic (SBP) and diastolic (DBP) BP and how these compared with determinants of daytime and night-time SBP and DBP. We analysed the association of mean daytime, mean night-time and mean day–night difference (defined as (mean daytime−mean night-time)/mean daytime) in SBP and DBP with clinical, lifestyle and biochemical parameters from 1562 adult individuals (mean age 38.6) from 509 nuclear families recruited in the GRAPHIC Study. We estimated the heritability of the various BP phenotypes. In multivariate analysis, there were significant associations of age, sex, markers of adiposity (body mass index and waist–hip ratio), plasma lipids (total and low-density lipoprotein cholesterol and triglycerides), serum uric acid, alcohol intake and current smoking status on daytime or night-time SBP and/or DBP. Of these, only age (P=4.7 × 10−5), total cholesterol (P=0.002), plasma triglycerides (P=0.006) and current smoking (P=3.8 × 10−9) associated with day–night difference in SBP, and age (P=0.001), plasma triglyceride (P=2.2 × 10−5) and current smoking (3.8 × 10−4) associated with day–night difference in DBP. 24-h, daytime and night-time SBP and DBP showed substantial heritability (ranging from 18–43%). In contrast day–night difference in SBP showed a lower heritability (13%) while heritability of day–night difference in DBP was not significant. These data suggest that specific clinical, lifestyle and biochemical factors contribute to inter-individual variation in daytime, night-time and day–night differences in SBP and DBP. Variation in day–night differences in BP is largely non-genetic. PMID:26984683

Genetic parameters for milk mineral content and acidity predicted by mid-infrared spectroscopy in Holstein-Friesian cows.

PubMed

Toffanin, V; Penasa, M; McParland, S; Berry, D P; Cassandro, M; De Marchi, M

2015-05-01

The aim of the present study was to estimate genetic parameters for calcium (Ca), phosphorus (P) and titratable acidity (TA) in bovine milk predicted by mid-IR spectroscopy (MIRS). Data consisted of 2458 Italian Holstein-Friesian cows sampled once in 220 farms. Information per sample on protein and fat percentage, pH and somatic cell count, as well as test-day milk yield, was also available. (Co)variance components were estimated using univariate and bivariate animal linear mixed models. Fixed effects considered in the analyses were herd of sampling, parity, lactation stage and a two-way interaction between parity and lactation stage; an additive genetic and residual term were included in the models as random effects. Estimates of heritability for Ca, P and TA were 0.10, 0.12 and 0.26, respectively. Positive moderate to strong phenotypic correlations (0.33 to 0.82) existed between Ca, P and TA, whereas phenotypic weak to moderate correlations (0.00 to 0.45) existed between these traits with both milk quality and yield. Moderate to strong genetic correlations (0.28 to 0.92) existed between Ca, P and TA, and between these predicted traits with both fat and protein percentage (0.35 to 0.91). The existence of heritable genetic variation for Ca, P and TA, coupled with the potential to predict these components for routine cow milk testing, imply that genetic gain in these traits is indeed possible.

Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study

PubMed Central

Gribble, Matthew O.; Voruganti, Venkata Saroja; Cole, Shelley A.; Haack, Karin; Balakrishnan, Poojitha; Laston, Sandra L.; Tellez-Plaza, Maria; Francesconi, Kevin A.; Goessler, Walter; Umans, Jason G.; Thomas, Duncan C.; Gilliland, Frank; North, Kari E.; Franceschini, Nora; Navas-Acien, Ana

2015-01-01

Arsenic toxicokinetics are important for disease risks in exposed populations, but genetic determinants are not fully understood. We examined urine arsenic species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study participants 18 years of age and older with data on ∼400 genome-wide microsatellite markers spaced ∼10 cM and arsenic speciation (683 participants from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit-transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also conducted principal component analyses of the logit % arsenic species. We used inverse-normalized residuals from multivariable-adjusted polygenic heritability analysis for multipoint variance components linkage analysis. We also examined the contribution of polymorphisms in the arsenic metabolism gene AS3MT via conditional linkage analysis. We localized a quantitative trait locus (QTL) on chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal component of logit % arsenic species). This peak was partially but not fully explained by measured AS3MT variants. We also localized a QTL for the second principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that was not evident from considering % arsenic species individually. Some other loci were suggestive or significant for 1 geographical area but not overall across all areas, indicating possible locus heterogeneity. This genome-wide linkage scan suggests genetic determinants of arsenic toxicokinetics to be identified by future fine-mapping, and illustrates the utility of principal component analysis as a novel approach that considers % arsenic species jointly. PMID:26209557

On the reconciliation of missing heritability for genome-wide association studies

PubMed Central

Chen, Guo-Bo

2016-01-01

The definition of heritability has been unique and clear, but its estimation and estimates vary across studies. Linear mixed model (LMM) and Haseman–Elston (HE) regression analyses are commonly used for estimating heritability from genome-wide association data. This study provides an analytical resolution that can be used to reconcile the differences between LMM and HE in the estimation of heritability given the genetic architecture, which is responsible for these differences. The genetic architecture was classified into three forms via thought experiments: (i) coupling genetic architecture that the quantitative trait loci (QTLs) in the linkage disequilibrium (LD) had a positive covariance; (ii) repulsion genetic architecture that the QTLs in the LD had a negative covariance; (iii) and neutral genetic architecture that the QTLs in the LD had a covariance with a summation of zero. The neutral genetic architecture is so far most embraced, whereas the coupling and the repulsion genetic architecture have not been well investigated. For a quantitative trait under the coupling genetic architecture, HE overestimated the heritability and LMM underestimated the heritability; under the repulsion genetic architecture, HE underestimated but LMM overestimated the heritability for a quantitative trait. These two methods gave identical results under the neutral genetic architecture. A general analytical result for the statistic estimated under HE is given regardless of genetic architecture. In contrast, the performance of LMM remained elusive, such as further depended on the ratio between the sample size and the number of markers, but LMM converged to HE with increased sample size. PMID:27436266

Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder

PubMed Central

2013-01-01

Schizophrenia (SCZ) is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits with heritability estimated at up to 80%1,2. We adopted two analytic approaches to determine the extent to which common genetic variation underlies risk of SCZ using genome-wide association study (GWAS) data from 3,322 European individuals with SCZ and 3,587 controls. First, we implicate the major histocompatibility complex (MHC). Second, we provide molecular genetic evidence for a substantial polygenic component to risk of SCZ involving thousands of common alleles of very small effect. We show that this component also contributes to risk of bipolar disorder (BPD), but not to multiple non-psychiatric diseases. PMID:19571811

Cold Pressor Pain Sensitivity in Twins Discordant for Chronic Fatigue Syndrome

PubMed Central

Ullrich, Phil; Afari, Niloofar; Jacobsen, Clemma; Goldberg, Jack; Buchwald, Dedra

2010-01-01

Objective Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS. Design Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS. Patients and Setting Fifteen twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington. Results Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (p = 0.003) and fatigue (p < 0.001) by their cotwins without CFS. Conclusions These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS. PMID:17371408

Gene-gene and gene-environment interactions defining lipid-related traits.

PubMed

Ordovás, José M; Robertson, Ruairi; Cléirigh, Ellen Ní

2011-04-01

Steps towards reducing chronic disease progression are continuously being taken through the form of genomic research. Studies over the last year have highlighted more and more polymorphisms, pathways and interactions responsible for metabolic disorders such as cardiovascular disease, obesity and dyslipidemia. Many of these chronic illnesses can be partially blamed by altered lipid metabolism, combined with individual genetic components. Critical evaluation and comparison of these recent studies is essential in order to comprehend the results, conclusions and future prospects in the field of genomics as a whole. Recent literature elucidates significant gene--diet and gene--environment interactions resulting in altered lipid metabolism, inflammation and other metabolic imbalances leading to cardiovascular disease and obesity. Epigenetic and epistatic interactions are now becoming more significantly associated with such disorders, as genomic research digs deeper into the complex nature of genetic individuality and heritability. The vast array of data collected from genome-wide association studies must now be empowered and explored through more complex interaction studies, using standardized methods and larger sample sizes. In doing so the etiology of chronic disease progression will be further understood.

Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region: an individual-based pooled analysis of 40 twin cohorts.

PubMed

Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie; Hur, Yoon-Mi; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Tomizawa, Rie; Pietiläinen, Kirsi H; Rissanen, Aila; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Piirtola, Maarit; Aaltonen, Sari; Öncel, Sevgi Y; Aliev, Fazil; Rebato, Esther; Hjelmborg, Jacob B; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Silberg, Judy L; Eaves, Lindon J; Cutler, Tessa L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E; Kremen, William S; Lyons, Michael J; Busjahn, Andreas; Nelson, Tracy L; Whitfield, Keith E; Kandler, Christian; Jang, Kerry L; Gatz, Margaret; Butler, David A; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E; Buchwald, Dedra; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Jeong, Hoe-Uk; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L; Dahl Aslan, Anna K; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Spector, Timothy D; Mangino, Massimo; Lachance, Genevieve; Burt, S Alexandra; Klump, Kelly L; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Corley, Robin P; Huibregtse, Brooke M; Bartels, Meike; van Beijsterveldt, Catharina Em; Willemsen, Gonneke; Goldberg, Jack H; Rasmussen, Finn; Tarnoki, Adam D; Tarnoki, David L; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth Jf; Hopper, John L; Sung, Joohon; Maes, Hermine H; Turkheimer, Eric; Boomsma, Dorret I; Sørensen, Thorkild Ia; Kaprio, Jaakko

2017-08-01

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m 2 )], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population. © 2017 American Society for Nutrition.

Incorporation of economic values into the component traits of a ratio: feed efficiency.

PubMed

Lin, C Y; Aggrey, S E

2013-04-01

Direct selection on a ratio (R) of 2 traits (x1/x2) does not have a mechanism to accommodate the relative economic values (a1 and a2) between x1 and x2 because selection criteria x1/x2 and a1x1/a2x2 rank animals in the same order. This study presented a procedure to incorporate the economic weights into ratio traits through linear transformation. The partial derivatives of a nonlinear profit function evaluated at the means were widely taken as economic weights in the literature. This study showed that the economic weights derived in this manner were erroneous because they actually contain a mixture of actual economic weights and transformation effects. The ratios 1/2 and 2/4 are considered equal by selection on R, but are treated differently by the linear index. In addition, this study presented a unified approach to compare 4 different selection strategies for genetic improvement of ratio traits: linear index (I), selection on the ratio (R), selection on difference between x1 and x2 (D), and selection on x1 alone. This study considered 3 levels of heritability each for variables x1 and x2 and 2 levels of genetic correlations (γG), 2 ratios of means (µ1/µ2), and 4 ratios of phenotypic variances giving a total of 96 scenarios. Linear index I was the most efficient of the 4 criteria compared in all 96 scenarios studied. The superiority of index I over R, D, and selection on x1 alone are particularly remarkable when x1 and x2 have a large difference in heritability and are highly correlated. Selection on x1 alone is an economically viable alternative to criterion I or R for the improvement of ratio traits particularly when x1 is more heritable than x2 and when x2 is costly to measure. Selection on D is more efficient than direct selection on R or selection on x1 alone when x1 is less heritable than x2 and the difference between µ1 and µ2 is small.

Gene-environment interaction in atopic diseases: a population-based twin study of early-life exposures.

PubMed

Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke; Bønnelykke, Klaus; Thomsen, Simon Francis

2015-01-01

The development of atopic diseases early in life suggests an important role of perinatal risk factors. To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. © 2014 John Wiley & Sons Ltd.

Quantitative genetic analysis of agronomic and morphological traits in sorghum, Sorghum bicolor

PubMed Central

Mohammed, Riyazaddin; Are, Ashok K.; Bhavanasi, Ramaiah; Munghate, Rajendra S.; Kavi Kishor, Polavarapu B.; Sharma, Hari C.

2015-01-01

The productivity in sorghum is low, owing to various biotic and abiotic constraints. Combining insect resistance with desirable agronomic and morphological traits is important to increase sorghum productivity. Therefore, it is important to understand the variability for various agronomic traits, their heritabilities and nature of gene action to develop appropriate strategies for crop improvement. Therefore, a full diallel set of 10 parents and their 90 crosses including reciprocals were evaluated in replicated trials during the 2013–14 rainy and postrainy seasons. The crosses between the parents with early- and late-flowering flowered early, indicating dominance of earliness for anthesis in the test material used. Association between the shoot fly resistance, morphological, and agronomic traits suggested complex interactions between shoot fly resistance and morphological traits. Significance of the mean sum of squares for GCA (general combining ability) and SCA (specific combining ability) of all the studied traits suggested the importance of both additive and non-additive components in inheritance of these traits. The GCA/SCA, and the predictability ratios indicated predominance of additive gene effects for majority of the traits studied. High broad-sense and narrow-sense heritability estimates were observed for most of the morphological and agronomic traits. The significance of reciprocal combining ability effects for days to 50% flowering, plant height and 100 seed weight, suggested maternal effects for inheritance of these traits. Plant height and grain yield across seasons, days to 50% flowering, inflorescence exsertion, and panicle shape in the postrainy season showed greater specific combining ability variance, indicating the predominance of non-additive type of gene action/epistatic interactions in controlling the expression of these traits. Additive gene action in the rainy season, and dominance in the postrainy season for days to 50% flowering and plant height suggested G X E interactions for these traits. PMID:26579183

Environmental and genetic sources of diversification in the timing of seed germination: implications for the evolution of bet hedging.

PubMed

Simons, Andrew M; Johnston, Mark O

2006-11-01

Environmental variation that is not predictably related to cues is expected to drive the evolution of bet-hedging strategies. The high variance observed in the timing of seed germination has led to it being the most cited diversification strategy in the theoretical bet-hedging literature. Despite this theoretical focus, virtually nothing is known about the mechanisms responsible for the generation of individual-level diversification. Here we report analyses of sources of variation in timing of germination within seasons, germination fraction over two generations and three sequential seasons, and the genetic correlation structure of these traits using almost 10,000 seeds from more than 100 genotypes of the monocarpic perennial Lobelia inflata. Microenvironmental analysis of time to germination suggests that extreme sensitivity to environmental gradients, or microplasticity, even within a homogeneous growth chamber, may act as an effective individual-level diversification mechanism and explains more than 30% of variance in time to germination. The heritability of within-season timing of germination was low (h(2) = 0.07) but significant under homogeneous conditions. Consistent with individual-level diversification, this low h(2) was attributable not to low additive genetic variance, but to an unusually high coefficient of residual variation in time to germination. Despite high power to detect additive genetic variance in within-season diversification, it was low and indistinguishable from zero. Restricted maximum likelihood detected significant genetic variation for germination fraction (h(2) = 0.18) under homogeneous conditions. Unexpectedly, this heritability was positive when measured within a generation by sibling analysis and negative when measured across generations by offspring-on-parent regression. The consistency of dormancy fraction over multiple delays, a major premise of Cohen's classic model, was supported by a strong genetic correlation (r = 0.468) observed for a cohort's germination fraction over two seasons. We discuss implications of the results for the evolution of bet hedging and highlight the need for further empirical study of the causal components of diversification.

Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

PubMed Central

Alam, Imranul; Koller, Daniel L.; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J.; Turner, Charles H.; Foroud, Tatiana

2011-01-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high-resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from 5 of the 8 progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. PMID:21334473

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

PubMed

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright © 2010 Elsevier Inc. All rights reserved.

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL).

PubMed

Morrison, Jean; Laurie, Cathy C; Marazita, Mary L; Sanders, Anne E; Offenbacher, Steven; Salazar, Christian R; Conomos, Matthew P; Thornton, Timothy; Jain, Deepti; Laurie, Cecelia A; Kerr, Kathleen F; Papanicolaou, George; Taylor, Kent; Kaste, Linda M; Beck, James D; Shaffer, John R

2016-02-15

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18-74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20-53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10(-10)), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10(-8)) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Age trends in genetic control of Juglans nigra L. height growth

Treesearch

George Rink; F. H. Kung

1995-01-01

Age-related trends in narrow-sense and family heritabilities for black walnut height and dbh from a southern Illinois open-pollinated progeny test are evaluated through age 20 years. Narrow-sense heritability for height tends to be relatively stable between ages 10 and 20 at 0.55 - 0.65 with similar patterns and values for family heritabilities for both height and dbh...

Genetics of Nicotine Dependence and Pharmacotherapy

PubMed Central

Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

2008-01-01

Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

Hip dysplasia in labrador retrievers: the effects of age at scoring.

PubMed

Wood, J L N; Lakhani, K H

2003-01-11

Selective breeding policies for preventing or controlling hip dysplasia require accurate estimates of parameters in offspring/parental relationships and estimates of heritability. Recent literature includes some major studies of pedigree breeds of dog, using data derived from the hip dysplasia screening scheme set up by the British Veterinary Association. These publications have not taken into account the age of the animals when they were screened. This study analyses the data from 29,213 labrador retrievers whose ages were known when they screened. The mean hip score of the dogs was positively and significantly correlated with their age. If this relationship with age is ignored, various offspring/parental relationships and the estimates of heritability are likely to be distorted.

Cancer Chemoprotection Through Nutrient-mediated Histone Modifications

PubMed Central

Gao, Yifeng; Tollefsbol, Trygve O.

2016-01-01

Epigenetics, the study of heritable changes in gene expression without modifying the nucleotide sequence, is among the most important topics in medicinal chemistry and cancer chemoprotection. Among those changes, DNA methylation and histone modification have been shown to be associated with various types of cancers in a number of ways, many of which are regulated by dietary components that are mostly found in plants. Although, mechanisms of nutrient components affecting histone acetylation/deacetylation in cancer are widely studied, how those natural compounds affect cancer through other histone modifications, such as methylation, phosphorylation and ubiquitylation, is rarely reviewed. Thus, this review article discusses impacts recently studied on histone acetylation as well as other histone modifications by dietary components, such as genistein, resveratrol, curcumin, epigallocatechin-3-gallate (EGCG), 3,3′-diindolylmethane (DIM), diallyl disulfide, garcinol, procyanidin B3, quercetin, sulforaphane and other isothiocyanates, in various types of cancer. PMID:25891109

Early warm-rewarding parenting moderates the genetic contributions to callous-unemotional traits in childhood.

PubMed

Henry, Jeffrey; Dionne, Ginette; Viding, Essi; Vitaro, Frank; Brendgen, Mara; Tremblay, Richard E; Boivin, Michel

2018-04-23

Previous gene-environment interaction studies of CU traits have relied on the candidate gene approach, which does not account for the entire genetic load of complex phenotypes. Moreover, these studies have not examined the role of positive environmental factors such as warm/rewarding parenting. The aim of the present study was to determine whether early warm/rewarding parenting moderates the genetic contributions (i.e., heritability) to callous-unemotional (CU) traits at school age. Data were collected in a population sample of 662 twin pairs (Quebec Newborn Twin Study - QNTS). Mothers reported on their warm/rewarding parenting. Teachers assessed children's CU traits. These reports were subjected to twin modeling. Callous-unemotional traits were highly heritable, with the remaining variance accounted for by nonshared environmental factors. Warm/rewarding parenting significantly moderated the role of genes in CU traits; heritability was lower when children received high warm/rewarding parenting than when they were exposed to low warm/rewarding parenting. High warm/rewarding parenting may partly impede the genetic expression of CU traits. Developmental models of CU traits need to account for such gene-environment processes. © 2018 Association for Child and Adolescent Mental Health.

Shared etiology of phonological memory and vocabulary deficits in school-age children.

PubMed

Peterson, Robin L; Pennington, Bruce F; Samuelsson, Stefan; Byrne, Brian; Olson, Richard K

2013-08-01

The goal of this study was to investigate the etiologic basis for the association between deficits in phonological memory (PM) and vocabulary in school-age children. Children with deficits in PM or vocabulary were identified within the International Longitudinal Twin Study (ILTS; Samuelsson et al., 2005). The ILTS includes 1,045 twin pairs (between the ages of 5 and 8 years) from the United States, Australia, and Scandinavia. The authors applied the DeFries-Fulker ( DeFries & Fulker, 1985, 1988) regression method to determine whether problems in PM and vocabulary tend to co-occur because of overlapping genes, overlapping environmental risk factors, or both. Among children with isolated PM deficits, the authors found significant bivariate heritability of PM and vocabulary weaknesses both within and across time. However, when probands were selected for a vocabulary deficit, there was no evidence for bivariate heritability. In this case, it appears that the PM-vocabulary relationship is caused by common shared environmental experiences. The findings are consistent with previous research on the heritability of specific language impairment and suggest that there are etiologic subgroups of children with low vocabulary for different reasons, 1 being more influenced by genes and another being more influenced by environment.

Heritability of hair whorl position on the forehead in Konik horses.

PubMed

Górecka, A; Słoniewski, K; Golonka, M; Jaworski, Z; Jezierski, T

2006-12-01

There are studies on the relationship between the position and shape of hair whorls on bovine forehead and phenotypic traits. According to anecdotal beliefs by horse users and handlers, temperamental traits may be related to the position of hair whorls in horses. No previous research on the mechanisms of inheritance of hair whorls has been performed, so the aim of the present study was to determine the heritability of the position of the hair whorl on the forehead of Konik horses. The horses (n = 362) were classified into five groups based on the whorl position on forehead with respect to the top and bottom eye lines. The estimated heritability of hair whorl position was 0.753 (SE = 0.056). Heritability adjusted for the discontinuity of the trait was 0.836. The results show that hair whorl position in Konik Polski horses is highly heritable. The possible relationship between position of hair whorls on the forehead and other morphological traits needs further research and should be interpreted with caution.

Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index

PubMed Central

Yang, Jian; Bakshi, Andrew; Zhu, Zhihong; Hemani, Gibran; Vinkhuyzen, Anna A.E.; Lee, Sang Hong; Robinson, Matthew R.; Perry, John R.B.; Nolte, Ilja M.; van Vliet-Ostaptchouk, Jana V.; Snieder, Harold; Esko, Tonu; Milani, Lili; Mägi, Reedik; Metspalu, Andres; Hamsten, Anders; Magnusson, Patrik K.E.; Pedersen, Nancy L.; Ingelsson, Erik; Soranzo, Nicole; Keller, Matthew C.; Wray, Naomi R.; Goddard, Michael E.; Visscher, Peter M.

2015-01-01

We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing (WGS) data. We demonstrate using simulations based on WGS data that ~97% and ~68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all ~17M imputed variants explain 56% (s.e. = 2.3%) of variance for height and 27% (s.e. = 2.5%) for body mass index (BMI), and find evidence that height- and BMI-associated variants have been under natural selection. Considering imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60–70% for height and 30–40% for BMI. Therefore, missing heritability is small for both traits. For further gene discovery of complex traits, a design with SNP arrays followed by imputation is more cost-effective than WGS at current prices. PMID:26323059

Exploring the Genetic Etiology of Trust in Adolescents: Combined Twin and DNA Analyses.

PubMed

Wootton, Robyn E; Davis, Oliver S P; Mottershaw, Abigail L; Wang, R Adele H; Haworth, Claire M A

2016-12-01

Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom's Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene-environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust.

Exploring the Genetic Etiology of Trust in Adolescents: Combined Twin and DNA Analyses

PubMed Central

Wootton, Robyn E.; Davis, Oliver S. P.; Mottershaw, Abigail L.; Wang, R. Adele H.; Haworth, Claire M. A.

2017-01-01

Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom’s Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene–environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust. PMID:27852354

Egg shell quality in Japanese quail: characteristics, heritabilities and genetic and phenotypic relationships.

PubMed

Narinc, D; Aygun, A; Karaman, E; Aksoy, T

2015-07-01

The objective of the present study was to estimate heritabilities as well as genetic and phenotypic correlations for egg weight, specific gravity, shape index, shell ratio, egg shell strength, egg length, egg width and shell weight in Japanese quail eggs. External egg quality traits were measured on 5864 eggs of 934 female quails from a dam line selected for two generations. Within the Bayesian framework, using Gibbs Sampling algorithm, a multivariate animal model was applied to estimate heritabilities and genetic correlations for external egg quality traits. The heritability estimates for external egg quality traits were moderate to high and ranged from 0.29 to 0.81. The heritability estimates for egg and shell weight of 0.81 and 0.76 were fairly high. The genetic and phenotypic correlations between egg shell strength with specific gravity, shell ratio and shell weight ranging from 0.55 to 0.79 were relatively high. It can be concluded that it is possible to determine egg shell quality using the egg specific gravity values utilizing its high heritability and fairly high positive correlation with most of the egg shell quality traits. As a result, egg specific gravity may be the choice of selection criterion rather than other external egg traits for genetic improvement of egg shell quality in Japanese quails.

Keeping pace with climate change: what is wrong with the evolutionary potential of upper thermal limits?

PubMed Central

Santos, Mauro; Castañeda, Luis E; Rezende, Enrico L

2012-01-01

The potential of populations to evolve in response to ongoing climate change is partly conditioned by the presence of heritable genetic variation in relevant physiological traits. Recent research suggests that Drosophila melanogaster exhibits negligible heritability, hence little evolutionary potential in heat tolerance when measured under slow heating rates that presumably mimic conditions in nature. Here, we study the effects of directional selection for increased heat tolerance using Drosophila as a model system. We combine a physiological model to simulate thermal tolerance assays with multilocus models for quantitative traits. Our simulations show that, whereas the evolutionary response of the genetically determined upper thermal limit (CTmax) is independent of methodological context, the response in knockdown temperatures varies with measurement protocol and is substantially (up to 50%) lower than for CTmax. Realized heritabilities of knockdown temperature may grossly underestimate the true heritability of CTmax. For instance, assuming that the true heritability of CTmax in the base population is h2 = 0.25, realized heritabilities of knockdown temperature are around 0.08–0.16 depending on heating rate. These effects are higher in slow heating assays, suggesting that flawed methodology might explain the apparently limited evolutionary potential of cosmopolitan D. melanogaster. PMID:23170220

Heritability of Transforming Growth Factor-β1 and Tumor Necrosis Factor-Receptor Type 1 Expression and Vitamin D Levels in Healthy Adolescent Twins.

PubMed

Mills, Natalie T; Wright, Margie J; Henders, Anjali K; Eyles, Darryl W; Baune, Bernhard T; McGrath, John J; Byrne, Enda M; Hansell, Narelle K; Birosova, Eva; Scott, James G; Martin, Nicholas G; Montgomery, Grant W; Wray, Naomi R; Vinkhuyzen, Anna A E

2015-02-01

Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26-0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11-0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61-0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.