A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood

PubMed Central

Reichborn-Kjennerud, T.; Czajkowski, N.; Ystrøm, E.; Ørstavik, R.; Aggen, S. H.; Tambs, K.; Torgersen, S.; Neale, M. C.; Røysamb, E.; Krueger, R. F.; Knudsen, G. P.; Kendler, K. S.

2015-01-01

Background Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. Method DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. Results The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. Conclusion ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD. PMID:26050739

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood.

PubMed

Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S

2015-10-01

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts.

PubMed

Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Fagnani, Corrado; Stazi, Maria A; Brescianini, Sonia; Ji, Fuling; Ning, Feng; Pang, Zengchang; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Rebato, Esther; Hopper, John L; Cutler, Tessa L; Saudino, Kimberly J; Nelson, Tracy L; Whitfield, Keith E; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Llewellyn, Clare H; Fisher, Abigail; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Bartels, Meike; van Beijsterveldt, Catharina E M; Willemsen, Gonneke; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Rasmussen, Finn; Tynelius, Per; Tarnoki, Adam D; Tarnoki, David L; Ooki, Syuichi; Rose, Richard J; Pietiläinen, Kirsi H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

2018-05-19

The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.

Adults' perceptions of genetic counseling and genetic testing.

PubMed

Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley

2015-02-01

This study described the perceptions of genetic counseling and testing of adults (N = 116) attending a genetic education program. Understanding perceptions of genetic counseling, including the importance of counseling topics, will contribute to patient-focused care as clinical genetic applications for common, complex disorders evolve. Participants completed a survey addressing: the importance of genetic counseling topics, benefits and negative effects of genetic testing, and sharing test results. Topics addressing practical information about genetic conditions were rated most important; topics involving conceptual genetic/genomic principles were rated least important. The most frequently identified benefit and negative effect of testing were prevention/early detection/treatment and psychological distress. Participants perceived that they were more likely to share test results with first-degree than other relatives. Findings suggest providing patients with practical information about genetic testing and genetic contributions to disease, while also determining whether their self-care abilities would be enhanced by teaching genetic/genomic principles. Copyright © 2014 Elsevier Inc. All rights reserved.

The genetic-environmental etiology of cognitive school readiness and later academic achievement in early childhood.

PubMed

Lemelin, Jean-Pascal; Boivin, Michel; Forget-Dubois, Nadine; Dionne, Ginette; Séguin, Jean R; Brendgen, Mara; Vitaro, Frank; Tremblay, Richard E; Pérusse, Daniel

2007-01-01

Using a genetic design of 840 60-month-old twins, this study investigated the genetic and environmental contributions to (a) individual differences in four components of cognitive school readiness, (b) the general ability underlying these four components, and (c) the predictive association between school readiness and school achievement. Results revealed that the contribution of the shared environment for cognitive school readiness was substantial. Genetic effects were more important for the core abilities underlying school readiness than for each specific skill, although shared environment remained the largest factor overall. Genetic, shared, and nonshared environmental factors all accounted for the predictive association between school readiness and early school achievement. These results contribute to a better understanding of the early determinants of school readiness.

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins

PubMed Central

Silberg, Judy L.; Gillespie, Nathan; Moore, Ashlee A.; Eaves, Lindon J.; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-01-01

Objective Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children. PMID:25728588

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

PubMed

Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-04-01

Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

PubMed Central

Prom-Wormley, Elizabeth; Eaves, Lindon J.; Rhee, Soo Hyun; Hewitt, John K.; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G.; Legrand, Lisa; Samek, Diana R.; Murrelle, E. Lenn; Silberg, Judy L.; Miles, Donna R.; Schieken, Richard M.; Beunen, Gaston P.; Thomis, Martine; Rose, Richard J.; Dick, Danielle M.; Boomsma, Dorret I.; Bartels, Meike; Vink, Jacqueline M.; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C.

2017-01-01

Abstract Introduction: Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Methods: Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Results: Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Conclusions: Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. Implications: This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. PMID:27807125

Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study

PubMed Central

Cui, Jeffrey; Chen, Chi-Hua; Lo, Min-Tzu; Schork, Nicholas; Bettencourt, Ricki; Gonzalez, Monica P; Bhatt, Archana; Hooker, Jonathan; Shaffer, Katherine; Nelson, Karen E; Long, Michelle T; Brenner, David A; Sirlin, Claude B; Loomba, Rohit

2016-01-01

Introduction Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic risk factors including hypertension and dyslipidemia, and may progress to liver fibrosis. Previous studies have shown that hepatic steatosis and fibrosis are heritable but whether they have a significant shared gene effect is unknown. This study aimed to examine the shared gene effects between hepatic steatosis, fibrosis, and their associations with metabolic risk factors. Methods This is a cross-sectional analysis of a prospective cohort of well-characterized, community-dwelling twins (45 monozygotic, 20 dizygotic twin pairs, 130 total subjects) from Southern California. Hepatic steatosis was assessed with MRI-proton density fat fraction (MRI-PDFF) and hepatic fibrosis was assessed with magnetic resonance elastography (MRE). A standard bivariate twin AE model was used to estimate the proportion of phenotypic variance between two phenotypes accounted for by additive genetic effects (A) and individual-specific environmental effects (E). Genetic correlations (rG) estimated from this model represent the degree to which the genetic determinants of two phenotypes overlap. Results The mean (±SD) age and BMI were 47.1 (±21.9) years and 26.9 (±6.5) kg/m2, respectively. 20% (26/130) of the cohort had hepatic steatosis (MRI-PDFF ≥5%) and 8.2% (10/122) had hepatic fibrosis (MRE ≥3Kpa). Blood pressure (systolic and diastolic), triglycerides, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), insulin, hemoglobin A1c (HbA1c), and low high-density lipoprotein (HDL) had significant shared gene effects with hepatic steatosis. Triglycerides, glucose, HOMA-IR, insulin, HbA1c, and low HDL had significant shared gene effects with hepatic fibrosis. Hepatic steatosis and fibrosis had a highly significant shared gene effect of 0.756 (95% CI: 0.716–1, p<0.0001). Conclusions Genes involved with steatosis pathogenesis may also be involved with fibrosis pathogenesis. PMID:27315352

Crying without a cause and being easily upset in two-year-olds: heritability and predictive power of behavioral problems.

PubMed

Groen-Blokhuis, Maria M; Middeldorp, Christel M; M van Beijsterveldt, Catharina E; Boomsma, Dorret I

2011-10-01

In order to estimate the influence of genetic and environmental factors on 'crying without a cause' and 'being easily upset' in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28-.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems.

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.

A population-based study of anxiety as a precursor for depression in childhood and adolescence.

PubMed

Rice, Frances; van den Bree, Marianne B M; Thapar, Anita

2004-12-13

Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5-17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression.

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

PubMed Central

Klump, Kelly L.; O’Connor, Shannon M.; Hildebrandt, Britny A.; Keel, Pamela K.; Neale, Michael; Sisk, Cheryl L.; Boker, Steven; Burt, S. Alexandra

2016-01-01

Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood. PMID:27747142

Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

PubMed

Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

2014-03-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

PubMed Central

Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

2014-01-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at three discrete ages-15-, 18-, and 21-years-old. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PMID:24015689

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins

PubMed Central

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L.

2012-01-01

Background The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Method Structured interviews on 2814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and young adult follow-up (YAFU) yielded data on symptoms of depression, conduct disorder and adolescent and young adult suicidal ideation. Results Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. Conclusions These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. PMID:22646517

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins.

PubMed

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L

2012-08-01

The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Structured interviews on 2,814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU) yielded data on symptoms of depression, conduct disorder, and adolescent and young adult suicidal ideation. Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. © 2012 The American Association of Suicidology.

Experiences of college-age youths in families with a recessive genetic condition.

PubMed

Hern, Marcia J; Beery, Theresa A; Barry, Detrice G

2006-05-01

Growing up in a family with a recessive genetic condition can trigger questions about progeny effect. This study explored perceptions of family hardiness and information sharing by 18- to 21-year-olds about genetic risk. Semistructured interviews, the Family Hardiness Index (FHI), and a Family Information Sharing Analog Scale (FISAS) were used. Participants included 11 youths who had relatives with hemophilia and 4 with sickle cell anemia. Findings revealed seven themes: assimilating premature knowledge; caring for others, denying self; cautioning during development; experiencing continual sickness; feeling less than; magnifying transition experiences; and sustaining by faith. There was no significant correlation between total FHI and FISAS. However, there was a statistically significant difference in FISAS between genetic condition variance. Specifically, higher hardiness was found and information sharing correlated among college youths in families with hemophilia. Additional research can lead to nursing interventions to provide genetic information to youths in families for illness variance.

Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

PubMed

Hunt, E; Bornovalova, M A; Patrick, C J

2015-05-01

Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

Investigating Environmental Links Between Parent Depression and Child Depressive/Anxiety Symptoms Using an Assisted Conception Design

PubMed Central

Lewis, Gemma; Rice, Frances; Harold, Gordon T.; Collishaw, Stephan; Thapar, Anita

2011-01-01

Objective Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Method Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother–child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Results Significant associations between parent and child symptoms were found for genetically unrelated mother–child (r = 0.32, p < .001) and father–child (r = 0.17, p < .05) pairs and genetically related mother–child (r = 0.31, p < .001) and father–child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. Conclusions The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. PMID:21515194

Associations Between Fetal Growth and Self-Perceived Health Throughout Adulthood: A Co-twin Control Study.

PubMed

Mosing, Miriam A; Cnattingius, Sven; Gatz, Margaret; Neiderhiser, Jenae M; Pedersen, Nancy L

2016-05-01

The literature shows evidence for long-lasting effects of low birth weight (LBW) on many health outcomes, but little is known about effects on self-perceived health. Findings are mixed and studies are small, mostly focusing on LBW effects on health outcomes before adulthood. Further, as LBW and most health conditions including self-perceived health are partly heritable, associations between birth weight (BW) and adverse health outcomes may also be due to shared genetic as well as other (pre- and postnatal) unmeasured environmental influences. We explored LBW effects on self-perceived health in early and later adulthood using a very large and genetically informative sample of more than 50,000 Swedish twins. In addition, analyses within twin pairs (the co-twin control design) were used to examine potential associations between BW and the offspring's risk for poor self-perceived health independent of shared environmental or genetic factors, evidence which is critical for the understanding of underlying mechanisms. Results showed that lower BW was significantly associated with poorer self-perceived health during adulthood, although the effect size was small. Co-twin control analyses suggested that this increased risk may be due to shared underlying liability (environmental or genetic) rather than a direct effect of BW, but findings were not conclusive.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

PubMed

Lacourse, E; Boivin, M; Brendgen, M; Petitclerc, A; Girard, A; Vitaro, F; Paquin, S; Ouellet-Morin, I; Dionne, G; Tremblay, R E

2014-09-01

Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

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

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents.

PubMed

Maes, Hermine H; Prom-Wormley, Elizabeth; Eaves, Lindon J; Rhee, Soo Hyun; Hewitt, John K; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G; Legrand, Lisa; Samek, Diana R; Murrelle, E Lenn; Silberg, Judy L; Miles, Donna R; Schieken, Richard M; Beunen, Gaston P; Thomis, Martine; Rose, Richard J; Dick, Danielle M; Boomsma, Dorret I; Bartels, Meike; Vink, Jacqueline M; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C

2017-04-01

Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology.

PubMed

Wesseldijk, Laura W; Fedko, Iryna O; Bartels, Meike; Nivard, Michel G; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; Middeldorp, Christel M

2017-04-01

The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Aetiology of teenage childbearing: reasons for familial effects.

PubMed

Olausson, P O; Lichtenstein, P; Cnattingius, S

2000-03-01

The aims of the present study were to evaluate the contribution of the genetic and environmental factors to the risk of teenage childbearing, and to study whether life style, socio-economic conditions, and personality traits could explain possible familial effects. We linked two population-based registers: the Swedish Twin Register and the Swedish Medical Birth Register. The study covers female twin pairs born between 1953 and 1958, having their first infant before the age of 30 years (n = 1885). In order to separate familial effects from other environmental influences, and genetic effects from shared environmental effects, only complete twin pairs with known zygosity were included, in all 260 monozygotic and 370 dizygotic twin pairs. We used quantitative genetic analyses to evaluate the importance of genetic and environmental effects for liability to teenage childbearing. Logistic regression analyses were used to estimate the effects of life style, socio-economic situation, and personality on the probability of teenage childbearing, and to study whether psychosocial factors could explain possible familial effects. Fifty-nine percent (0-76%) of the variance in being a teenage mother was attributable to heritable factors; 0% (0-49%) was due to shared environmental factors; and 41% (23-67%) was explained by non-shared environmental factors. Thus, the data were consistent with the hypothesis that the familial aggregation of teenage childbearing is completely explained by genetic factors, although the alternative hypothesis that familial aggregation is entirely explained by shared environmental factors cannot be ruled out. Significant effects of smoking habits, housing conditions, and educational level were found in relation to liability to teenage childbearing. However, the familial effects on risk of teenage childbearing were not mediated through similarities in life style and socio-economic factors. When studying risk factors for teenage childbearing, it is recommended to include life style and socio-economic variables as well as information about family history of teenage childbearing. Twin Research (2000) 3, 23-27.

Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection.

PubMed

Tarnoki, David Laszlo; Tarnoki, Adam Domonkos; Medda, Emanuela; Littvay, Levente; Lazar, Zsofia; Toccaceli, Virgilia; Fagnani, Corrado; Stazi, Maria Antonietta; Nisticó, Lorenza; Brescianini, Sonia; Penna, Luana; Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio; Baracchini, Claudio; Meneghetti, Giorgio; Koller, Akos; Osztovits, Janos; Jermendy, Gyorgy; Preda, Istvan; Kiss, Robert Gabor; Karlinger, Kinga; Lannert, Agnes; Horvath, Tamas; Schillaci, Giuseppe; Molnar, Andrea Agnes; Garami, Zsolt; Berczi, Viktor; Horvath, Ildiko

2013-06-01

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FE(NO)) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FE(NO) levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FE(NO) was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aix(ao)) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FE(NO) and Aix(ao) were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FE(NO) with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FE(NO) and Aix(ao) (r = -0.17; 95%CI:-0.32,-0.02). FE(NO) showed a significant negative genetic correlation with Aix(ao) (r(g) = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FE(NO) are explained both by genetic and non-shared environmental effects. Covariance between FE(NO) and Aix(ao) is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.

Stability and change in temperament during adolescence.

PubMed

Ganiban, Jody M; Saudino, Kimberly J; Ulbricht, Jennifer; Neiderhiser, Jenae M; Reiss, David

2008-07-01

This study assessed genetic and environmental contributions to temperament during adolescence within the Nonshared Environment and Adolescent Development project (NEAD; D. Reiss, J. M. Neiderhiser, E. M. Hetherington, & R. Plomin, 2000). NEAD is a national study that includes twins and other sibling types who vary in regard to genetic relatedness. Seven hundred twenty sibling pairs (aged 12.1-13.5 years) participated at Time 1, and 395 sibling pairs (aged 14.7-16.2 years) participated again at Time 2. At both Times, mothers and fathers rated their children's temperament (emotionality, activity, sociability, and shyness). At Times 1 and 2, genetic and nonshared environmental factors accounted for variance in temperament, whereas shared environmental contributions were negligible. However, at Time 1, genetic contributions were inflated, and shared environmental contributions were masked if sibling contrast effects were not taken into account. At Time 2, sibling interaction effects had little impact on estimates of genetic and environmental contributions to temperament. Last, temperament stability was primarily explained by genetic factors, whereas both genetic and nonshared environmental factors accounted for change.

Genes, Culture and Conservatism-A Psychometric-Genetic Approach.

PubMed

Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M

2016-07-01

The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.

Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness.

PubMed

Kandler, Christian; Riemann, Rainer

2013-07-01

In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.

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

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

The gene-environmental architecture of the development of adolescent substance use.

PubMed

Vitaro, Frank; Dickson, Daniel J; Brendgen, Mara; Laursen, Brett; Dionne, Ginette; Boivin, Michel

2018-02-19

Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic-environmental architecture of substance use across adolescence. Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years. ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence. The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic.

The Geography of Recent Genetic Ancestry across Europe

PubMed Central

Ralph, Peter; Coop, Graham

2013-01-01

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2–12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. PMID:23667324

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

PubMed Central

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-01-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

Cross-Cultural Comparison of Genetic and Cultural Transmission of Smoking Initiation Using an Extended Twin Kinship Model.

PubMed

Maes, Hermine H; Morley, Kate; Neale, Michael C; Kendler, Kenneth S; Heath, Andrew C; Eaves, Lindon J; Martin, Nicholas G

2018-06-01

Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime 'ever' smoking measure was obtained from twins and relatives in the 'Virginia 30,000' sample and the 'Australian 25,000'. Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.

Examining the genetic and environmental associations among spelling, reading fluency, reading comprehension and a high stakes reading test in a combined sample of third and fourth grade students

PubMed Central

Little, Callie W.

2015-01-01

The present study is an examination of the genetic and environmental effects on the associations among reading fluency, spelling and earlier reading comprehension on a later reading comprehension outcome (FCAT) in a combined sample of 3rd and 4th grade students using data from the 2011-2012 school year of the Florida Twin project on Reading (Taylor et al., 2013). A genetically sensitive model was applied to the data with results indicating a common genetic component among all four measures, along with shared and non-shared environmental influences common between reading fluency, spelling and FCAT. PMID:26770052

Investigating environmental links between parent depression and child depressive/anxiety symptoms using an assisted conception design.

PubMed

Lewis, Gemma; Rice, Frances; Harold, Gordon T; Collishaw, Stephan; Thapar, Anita

2011-05-01

Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother-child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Significant associations between parent and child symptoms were found for genetically unrelated mother-child (r = 0.32, p < .001) and father-child (r = 0.17, p < .05) pairs and genetically related mother-child (r = 0.31, p < .001) and father-child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Longitudinal Stability in Genetic Effects on Children's Conversational Language Productivity

ERIC Educational Resources Information Center

DeThorne, Laura Segebart; Harlaar, Nicole; Petrill, Stephen A.; Deater-Deckard, Kirby

2012-01-01

Purpose: The authors examined the longitudinal stability of genetic and environmental influences on children's productive language sample measures during the early school-age years. Method: Twin study methodology with structural equation modeling was used to derive univariate estimates of additive genetic (A), shared environmental (C), and…

Adolescents' Relationships to Siblings and Mothers: A Multivariate Genetic Analysis.

ERIC Educational Resources Information Center

Bussell, Danielle A.; And Others

1999-01-01

Examined relative contributions of genetic and environmental influences to the covariation between sibling relationships and mother/adolescent relationships in 719 same-sex sibling pairs of varying degrees of genetic relatedness. Found that the overlapping effects of shared environment on the two relationship subsystems explained most of the…

Replication of genetic associations as pseudoreplication due to shared genealogy.

PubMed

Rosenberg, Noah A; Vanliere, Jenna M

2009-09-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

Replication of genetic associations as pseudoreplication due to shared genealogy

PubMed Central

Rosenberg, Noah A.; VanLiere, Jenna M.

2009-01-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered “pseudoreplicates” rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence. PMID:19191270

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

PubMed

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-02-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

PubMed Central

Yin, Xianyong; Wineinger, Nathan E.; Wang, Kai; Yue, Weihua; Norgren, Nina; Wang, Ling; Yao, Weiyi; Jiang, Xiaoyun; Wu, Bo; Cui, Yong; Shen, Changbing; Cheng, Hui; Zhou, Fusheng; Chen, Gang; Zuo, Xianbo; Zheng, Xiaodong; Fan, Xing; Wang, Hongyan; Wang, Lifang; Lee, Jimmy; Lam, Max; Tai, E. Shyong; Zhang, Zheng; Huang, Qiong; Sun, Liangdan; Xu, Jinhua; Yang, Sen; Wilhelmsen, Kirk C.; Liu, Jianjun; Schork, Nicholas J.; Zhang, Xuejun

2016-01-01

Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10−8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways. PMID:27091718

The genetic and environmental etiology of antisocial behavior from childhood to emerging adulthood.

PubMed

Tuvblad, Catherine; Narusyte, Jurgita; Grann, Martin; Sarnecki, Jerzy; Lichtenstein, Paul

2011-09-01

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

The genetic correlation between height and IQ: shared genes or assortative mating?

PubMed

Keller, Matthew C; Garver-Apgar, Christine E; Wright, Margaret J; Martin, Nicholas G; Corley, Robin P; Stallings, Michael C; Hewitt, John K; Zietsch, Brendan P

2013-04-01

Traits that are attractive to the opposite sex are often positively correlated when scaled such that scores increase with attractiveness, and this correlation typically has a genetic component. Such traits can be genetically correlated due to genes that affect both traits ("pleiotropy") and/or because assortative mating causes statistical correlations to develop between selected alleles across the traits ("gametic phase disequilibrium"). In this study, we modeled the covariation between monozygotic and dizygotic twins, their siblings, and their parents (total N = 7,905) to elucidate the nature of the correlation between two potentially sexually selected traits in humans: height and IQ. Unlike previous designs used to investigate the nature of the height-IQ correlation, the present design accounts for the effects of assortative mating and provides much less biased estimates of additive genetic, non-additive genetic, and shared environmental influences. Both traits were highly heritable, although there was greater evidence for non-additive genetic effects in males. After accounting for assortative mating, the correlation between height and IQ was found to be almost entirely genetic in nature. Model fits indicate that both pleiotropy and assortative mating contribute significantly and about equally to this genetic correlation.

An examination of environmental and genetic contributions to the determinants of suicidal behavior among male twins

PubMed Central

Smith, April Rose; Ribeiro, Jessica; Mikolajewski, Amy; Taylor, Jeanette; Joiner, Thomas; Iacono, William G.

2012-01-01

The purpose of the present study was to examine the relative association of genetic and environmental factors with individual differences in each of the proximal, jointly necessary, and sufficient causes for suicidal behavior, according to the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner, 2005). We examined data on derived scales measuring acquired capability, belongingness, and burdensomeness (the determinants of suicidal behavior, according to theory) from 348 adolescent male twins. Univariate biometrical models were used to estimate the magnitude of additive genetic (A), non-additive genetic (D), shared environmental (C), and nonshared environmental (E) effects associated with the variance in acquired capability, belongingness, and burdensomeness. The best fitting model for the acquired capability allowed for additive genetic and environmental effects, whereas the best fitting model for burdensomeness and belongingness allowed for shared and nonshared environmental effects. The present research extends prior work by specifying the environmental and genetic contributions to the components of the IPTS, and our findings suggest that belongingness and burdensomeness may be more appropriate targets for clinical intervention than acquired capability as these factors may be more malleable or amenable to change. PMID:22417928

Assembling networks of microbial genomes using linear programming.

PubMed

Holloway, Catherine; Beiko, Robert G

2010-11-20

Microbial genomes exhibit complex sets of genetic affinities due to lateral genetic transfer. Assessing the relative contributions of parent-to-offspring inheritance and gene sharing is a vital step in understanding the evolutionary origins and modern-day function of an organism, but recovering and showing these relationships is a challenging problem. We have developed a new approach that uses linear programming to find between-genome relationships, by treating tables of genetic affinities (here, represented by transformed BLAST e-values) as an optimization problem. Validation trials on simulated data demonstrate the effectiveness of the approach in recovering and representing vertical and lateral relationships among genomes. Application of the technique to a set comprising Aquifex aeolicus and 75 other thermophiles showed an important role for large genomes as 'hubs' in the gene sharing network, and suggested that genes are preferentially shared between organisms with similar optimal growth temperatures. We were also able to discover distinct and common genetic contributors to each sequenced representative of genus Pseudomonas. The linear programming approach we have developed can serve as an effective inference tool in its own right, and can be an efficient first step in a more-intensive phylogenomic analysis.

Genetic architecture of verbal abilities in children and adolescents.

PubMed

Hoekstra, Rosa A; Bartels, Meike; van Leeuwen, Marieke; Boomsma, Dorret I

2009-11-01

The etiology of individual differences in general verbal ability, verbal learning and letter and category fluency were examined in two independent samples of 9- and 18-year-old twin pairs and their siblings. In both age groups, we observed strong familial resemblance for general verbal ability and moderate familial resemblance for verbal learning, letter and category fluency. All familial resemblance was explained by genetic factors. There was significant covariance among the tests, which was stronger in magnitude in the adolescent cohort. The covariance was mainly explained by genetic effects shared by subtests, both in middle childhood and in late adolescence. In addition to a shared set of genes that influenced all phenotypes, there were also genetic influences specific to the different verbal phenotypes.

Narrow-sense heritability estimation of complex traits using identity-by-descent information.

PubMed

Evans, Luke M; Tahmasbi, Rasool; Jones, Matt; Vrieze, Scott I; Abecasis, Gonçalo R; Das, Sayantan; Bjelland, Douglas W; de Candia, Teresa R; Yang, Jian; Goddard, Michael E; Visscher, Peter M; Keller, Matthew C

2018-03-28

Heritability is a fundamental parameter in genetics. Traditional estimates based on family or twin studies can be biased due to shared environmental or non-additive genetic variance. Alternatively, those based on genotyped or imputed variants typically underestimate narrow-sense heritability contributed by rare or otherwise poorly tagged causal variants. Identical-by-descent (IBD) segments of the genome share all variants between pairs of chromosomes except new mutations that have arisen since the last common ancestor. Therefore, relating phenotypic similarity to degree of IBD sharing among classically unrelated individuals is an appealing approach to estimating the near full additive genetic variance while possibly avoiding biases that can occur when modeling close relatives. We applied an IBD-based approach (GREML-IBD) to estimate heritability in unrelated individuals using phenotypic simulation with thousands of whole-genome sequences across a range of stratification, polygenicity levels, and the minor allele frequencies of causal variants (CVs). In simulations, the IBD-based approach produced unbiased heritability estimates, even when CVs were extremely rare, although precision was low. However, population stratification and non-genetic familial environmental effects shared across generations led to strong biases in IBD-based heritability. We used data on two traits in ~120,000 people from the UK Biobank to demonstrate that, depending on the trait and possible confounding environmental effects, GREML-IBD can be applied to very large genetic datasets to infer the contribution of very rare variants lost using other methods. However, we observed apparent biases in these real data, suggesting that more work may be required to understand and mitigate factors that influence IBD-based heritability estimates.

Has the "Equal Environments" assumption been tested in twin studies?

PubMed

Eaves, Lindon; Foley, Debra; Silberg, Judy

2003-12-01

A recurring criticism of the twin method for quantifying genetic and environmental components of human differences is the necessity of the so-called "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins experience equally correlated environments). It has been proposed to test the EEA by stratifying twin correlations by indices of the amount of shared environment. However, relevant environments may also be influenced by genetic differences. We present a model for the role of genetic factors in niche selection by twins that may account for variation in indices of the shared twin environment (e.g., contact between members of twin pairs). Simulations reveal that stratification of twin correlations by amount of contact can yield spurious evidence of large shared environmental effects in some strata and even give false indications of genotype x environment interaction. The stratification approach to testing the equal environments assumption may be misleading and the results of such tests may actually be consistent with a simpler theory of the role of genetic factors in niche selection.

Sex differences in genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood.

PubMed

Seglem, Karoline B; Waaktaar, Trine; Ask, Helga; Torgersen, Svenn

2016-07-01

To estimate genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood, and test whether gender moderates these effects. Longitudinal twin cohort design. Population-based sample from Norway. A total of 2862 male and female twins, aged 14-22 years, were assessed at one (n = 881), two (n = 898) or three (n = 1083) occasions. The percentage of females was between 56 and 63 in the different age groups (in the different waves). Alcohol consumption was measured by two questionnaire items about frequency of alcohol use and frequency of being drunk. Additive genetic effects showed low to moderate contributions [proportion estimate, 95% confidence interval (CI) = range from 0.03 (0.00-0.14) to 0.49 (0.37-0.59) in males and from 0.09 (0.00-0.57) to 0.41 (0.24-0.58) in females] from adolescence to young adulthood, while environmental influences shared by twin pairs and contributing to twin similarity were moderate to highly influential during this developmental period [proportion estimate, 95% CI = range from 0.04 (0.00-0.13) to 0.45 (0.26-0.60) in males for shared environment in common with females, from 0.25 (0.09-0.42) to 0.54 (0.06-0.78) for shared environment specific to males and from 0.36 (0.20-0.52) to 0.51 (0.37-0.71) in females]. There was evidence of qualitative sex differences with shared environmental influences being largely sex-specific from middle adolescence onwards. Alcohol consumption from early adolescence to young adulthood appears to be influenced to a small to moderate degree by genetic factors and to a moderate to high degree by shared environmental factors (e.g. rearing influences, shared friends). The shared environmental factors influencing alcohol consumption appear to be largely gender-specific. © 2016 Society for the Study of Addiction.

Genetic and environmental influences on temperament in the first year of life: the Puerto Rico Infant Twin Study (PRINTS).

PubMed

Silberg, Judy L; Miguel, Vivian Febo San; Murrelle, E Lenn; Prom, Elizabeth; Bates, John E; Canino, Glorisa; Egger, Helen; Eaves, Lindon J

2005-08-01

Three dimensions of temperament -- difficult temperament, unadaptablility and unsociability -- were assessed in the first year of life by maternal interview in twins born in Puerto Rico during 2001 and 2002. Eight hundred and sixty-five eligible mothers (80%) were traced and interviewed. Model-fitting results showed that additive genetic factors and the individual specific environment contributed to variation in all three dimensions. In addition, the pattern of variances and correlations suggested that sibling contrast effects influence ratings of difficult temperament. Moderate effects of the shared environment contributed to ratings of adaptability and sociability. There was a significant genetic correlation between difficult temperament and unadaptability. Genetic and environmental effects do not differ significantly between boys and girls. The study is the first population-based study of Puerto Rican twins and one of few to attempt the assessment of behavior in the first year. Preliminary results for difficult temperament and sociability were consistent with those in other populations and ages. In contrast, a significant effect of the shared environment on the temperamental trait of unadaptability has not been reported previously.

Examining the role of common genetic variants on alcohol, tobacco, cannabis, and illicit drug dependence

PubMed Central

Palmer, RHC; Brick, L; Nugent, NR; Bidwell, LC; McGeary, JE; Knopik, VS; Keller, MC

2014-01-01

Background and Aims Twin and family studies suggest that genetic influences are shared across substances of abuse. However, despite evidence of heritability, genome-wide association and candidate gene studies have indicated numerous markers of limited effects, suggesting that much of the heritability remains missing. We estimated (1) the aggregate effect of common single nucleotide polymorphisms (SNPs) on multiple indicators of comorbid drug problems that are typically employed across community and population-based samples, and (2) the genetic covariance across these measures. Participants 2596 unrelated subjects from the “Study of Addiction: Genetics and Environment” provided information on alcohol, tobacco, cocaine, cannabis, and other illicit substance dependence. Phenotypic measures included: (1) a factor score based on DSM-IV drug dependence diagnoses (DD), (2) a factor score based on problem use (PU; i.e., 1+ DSM-IV symptoms), and (3) dependence vulnerability (DV; a ratio of DSM-IV symptoms to the number of substances used). Findings Univariate and bivariate Genome-wide complex trait analyses of this selected sample indicated that common SNPs explained 25-36% of the variance across measures, with DD and DV having the largest effects [h2SNP (CI)=0.36 (0.11-0.62) and 0.33(0.07-0.58), respectively; PU = 0.25 (-0.01-0.51)]. Genetic effects were shared across the three phenotypic measures of comorbid drug problems (rSNP; rDD-PU = 0.92 (0.76-1.00), rDD-DV = 0.97 (0.87-1.00), and rPU-DV = 0.96 (0.82-1.00)). Conclusion At least 20% of the variance in the generalized vulnerability to substance dependence is attributable to common single nucleotide polymorphisms. The additive effect of common single nucleotide polymorphisms is shared across important indicators of comorbid drug problems. PMID:25424661

Identification of genetic loci shared between schizophrenia and the Big Five personality traits.

PubMed

Smeland, Olav B; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr; Witoelar, Aree; Tesli, Martin; Hinds, David A; Tung, Joyce Y; Djurovic, Srdjan; Chen, Chi-Hua; Dale, Anders M; Andreassen, Ole A

2017-05-22

Schizophrenia is associated with differences in personality traits, and recent studies suggest that personality traits and schizophrenia share a genetic basis. Here we aimed to identify specific genetic loci shared between schizophrenia and the Big Five personality traits using a Bayesian statistical framework. Using summary statistics from genome-wide association studies (GWAS) on personality traits in the 23andMe cohort (n = 59,225) and schizophrenia in the Psychiatric Genomics Consortium cohort (n = 82,315), we evaluated overlap in common genetic variants. The Big Five personality traits neuroticism, extraversion, openness, agreeableness and conscientiousness were measured using a web implementation of the Big Five Inventory. Applying the conditional false discovery rate approach, we increased discovery of genetic loci and identified two loci shared between neuroticism and schizophrenia and six loci shared between openness and schizophrenia. The study provides new insights into the relationship between personality traits and schizophrenia by highlighting genetic loci involved in their common genetic etiology.

Speech sound disorder influenced by a locus in 15q14 region.

PubMed

Stein, Catherine M; Millard, Christopher; Kluge, Amy; Miscimarra, Lara E; Cartier, Kevin C; Freebairn, Lisa A; Hansen, Amy J; Shriberg, Lawrence D; Taylor, H Gerry; Lewis, Barbara A; Iyengar, Sudha K

2006-11-01

Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

Family Background Buys an Education in Minnesota but Not in Sweden

PubMed Central

Johnson, Wendy; Deary, Ian J.; Silventoinen, Karri; Tynelius, Per; Rasmussen, Finn

2010-01-01

Educational attainment, the highest degree or level of schooling obtained, is associated with important life outcomes, at both the individual level and the group level. Because of this, and because education is expensive, the allocation of education across society is an important social issue. A dynamic quantitative environmental-genetic model can help document the effects of social allocation patterns. We used this model to compare the moderating effect of general intelligence on the environmental and genetic factors that influence educational attainment in Sweden and the U.S. state of Minnesota. Patterns of genetic influence on educational outcomes were similar in these two regions, but patterns of shared environmental influence differed markedly. In Sweden, shared environmental influence on educational attainment was particularly important for people of high intelligence, whereas in Minnesota, shared environmental influences on educational attainment were particularly important for people of low intelligence. This difference may be the result of differing access to education: state-supported access (on the basis of ability) to a uniform higher-education system in Sweden, versus family-supported access to a more diverse higher-education system in the United States. PMID:20679521

Family background buys an education in Minnesota but not in Sweden.

PubMed

Johnson, Wendy; Deary, Ian J; Silventoinen, Karri; Tynelius, Per; Rasmussen, Finn

2010-09-01

Educational attainment, the highest degree or level of schooling obtained, is associated with important life outcomes, at both the individual level and the group level. Because of this, and because education is expensive, the allocation of education across society is an important social issue. A dynamic quantitative environmental-genetic model can help document the effects of social allocation patterns. We used this model to compare the moderating effect of general intelligence on the environmental and genetic factors that influence educational attainment in Sweden and the U.S. state of Minnesota. Patterns of genetic influence on educational outcomes were similar in these two regions, but patterns of shared environmental influence differed markedly. In Sweden, shared environmental influence on educational attainment was particularly important for people of high intelligence, whereas in Minnesota, shared environmental influences on educational attainment were particularly important for people of low intelligence. This difference may be the result of differing access to education: state-supported access (on the basis of ability) to a uniform higher-education system in Sweden versus family-supported access to a more diverse higher-education system in the United States.

Genetic and environmental bases of the interplay between magical ideation and personality.

PubMed

Brambilla, Paolo; Fagnani, Corrado; Cecchetto, Filippo; Medda, Emanuela; Bellani, Marcella; Salemi, Miriam; Picardi, Angelo; Stazi, Maria Antonietta

2014-02-28

Sub-threshold psychotic symptoms are quite commonly present in general population. Among these, Magical Ideation (MI) has been proved to be a valid predictor of psychosis. However, the genetic and environmental influences on the interplay between MI and personality have not fully been explored. A total of 534 adult twins from the population-based Italian Twin Register were assessed for MI using the MI Scale (MIS) and for personality with the temperament and character inventory (TCI). A Multivariate Cholesky model was applied with Mx statistical program. The best-fitting model showed that additive genetic and unshared environmental factors explain approximately the same proportion of variance in MI, whereas a less strong genetic influence on personality traits emerged. Relevant correlations between MI and specific personality traits (novelty seeking, cooperativeness, self-directedness, self-transcendence) were found, suggesting shared influences for MI and these traits. Both genetic and environmental factors explained these correlations, with genetic factors playing a predominant role. Moderate-to-substantial genetic effects on MI and personality were found. Shared genetic and environmental effects underlie the phenotypic correlation between MI (psychosis-proneness) and personality traits, i.e. self-directedness (negative association) and self-transcendence (positive association), potentially representing predictive markers of psychosis liability related to schizotypy and personality. © 2013 Published by Elsevier Ireland Ltd.

The Nature and Nurture of Melody: A Twin Study of Musical Pitch and Rhythm Perception.

PubMed

Seesjärvi, Erik; Särkämö, Teppo; Vuoksimaa, Eero; Tervaniemi, Mari; Peretz, Isabelle; Kaprio, Jaakko

2016-07-01

Both genetic and environmental factors are known to play a role in our ability to perceive music, but the degree to which they influence different aspects of music cognition is still unclear. We investigated the relative contribution of genetic and environmental effects on melody perception in 384 young adult twins [69 full monozygotic (MZ) twin pairs, 44 full dizygotic (DZ) twin pairs, 70 MZ twins without a co-twin, and 88 DZ twins without a co-twin]. The participants performed three online music tests requiring the detection of pitch changes in a two-melody comparison task (Scale) and key and rhythm incongruities in single-melody perception tasks (Out-of-key, Off-beat). The results showed predominantly additive genetic effects in the Scale task (58 %, 95 % CI 42-70 %), shared environmental effects in the Out-of-key task (61 %, 49-70 %), and non-shared environmental effects in the Off-beat task (82 %, 61-100 %). This highly different pattern of effects suggests that the contribution of genetic and environmental factors on music perception depends on the degree to which it calls for acquired knowledge of musical tonal and metric structures.

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.

Cognitive, Noncognitive, and Family Background Contributions to College Attainment: A Behavioral Genetic Perspective.

PubMed

McGue, Matt; Rustichini, Aldo; Iacono, William G

2017-02-01

There is considerable evidence that college attainment is associated with family background and cognitive and noncognitive skills. Behavioral genetic methods are used to determine whether the family background effect is mediated through cognitive and noncognitive skill development. We analyze data from two longitudinal behavioral genetic studies: the Minnesota Twin Family Study, consisting of 1,382 pairs of like-sex twins and their parents, and the Sibling Interaction and Behavior Study, consisting of 409 adoptive and 208 nonadoptive families with two offspring and their rearing parents. Cognitive ability, noncognitive skills, and family background are all associated with offspring college attainment. Biometric analysis shows that the intergenerational transmission of college attainment owes to both genetic and shared environmental factors. The shared environmental influence was not due to highly educated parents fostering noncognitive skill development in their children, and there was limited evidence that they foster cognitive skill development. The environmental transmission of educational attainment does not appear to be a consequence of highly educated parents fostering cognitive and noncognitive skill development. Alternative mechanisms are needed to explain the strong shared environmental influence on college attainment. Possibilities include academic expectations, social network effects, and the economic benefits of having wealthy parents. © 2015 Wiley Periodicals, Inc.

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants

PubMed Central

Bagley, Steven C.; Sirota, Marina; Chen, Richard; Butte, Atul J.; Altman, Russ B.

2016-01-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups. PMID:27115429

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

PubMed

Bagley, Steven C; Sirota, Marina; Chen, Richard; Butte, Atul J; Altman, Russ B

2016-04-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Behavioural changes, sharing behaviour and psychological responses after receiving direct-to-consumer genetic test results: a systematic review and meta-analysis.

PubMed

Stewart, Kelly F J; Wesselius, Anke; Schreurs, Maartje A C; Schols, Annemie M W J; Zeegers, Maurice P

2018-01-01

It has been hypothesised that direct-to-consumer genetic tests (DTC-GTs) could stimulate health behaviour change. However, genetic testing may also lead to anxiety and distress or unnecessarily burden the health care system. The aim is to review and meta-analyse the effects of DTC-GT on (1) behaviour change, (2) psychological response and (3) medical consumption. A systematic literature search was performed in three databases, using "direct-to-consumer genetic testing" as a key search term. Random effects meta-analyses were performed when at least two comparable outcomes were available. After selection, 19 articles were included involving 11 unique studies. Seven studies involved actual consumers who paid the retail price, whereas four included participants who received free genetic testing as part of a research trial (non-actual consumers). In meta-analysis, 23% had a positive lifestyle change. More specifically, improved dietary and exercise practices were both reported by 12%, whereas 19% quit smoking. Seven percent of participants had subsequent preventive checks. Thirty-three percent shared their results with any health care professional and 50% with family and/or friends. Sub-analyses show that behaviour change was more prevalent among non-actual consumers, whereas sharing was more prevalent among actual consumers. Results on psychological responses showed that anxiety, distress and worry were low or absent and that the effect faded with time. DTC-GT has potential to be effective as a health intervention, but the right audience needs to be addressed with tailored follow-up. Research is needed to identify consumers who do and do not change behaviour or experience adverse psychological responses.

Genetic and environmental effects on age at menarche, and its relationship with reproductive health in twins.

PubMed

Jahanfar, Shayesteh; Lye, Munn-Sann; Krishnarajah, Isthrinayagy S

2013-04-01

Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors. Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche. A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers' formula and maximum likelihood. Heritability was found to be 66% using Falconers' formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%). Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins. It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.

Genetic and environmental influences on thin-ideal internalization.

PubMed

Suisman, Jessica L; O'Connor, Shannon M; Sperry, Steffanie; Thompson, J Kevin; Keel, Pamela K; Burt, S Alexandra; Neale, Michael; Boker, Steven; Sisk, Cheryl; Klump, Kelly L

2012-12-01

Current research on the etiology of thin-ideal internalization focuses on psychosocial influences (e.g., media exposure). The possibility that genetic influences also account for variance in thin-ideal internalization has never been directly examined. This study used a twin design to estimate genetic effects on thin-ideal internalization and examine if environmental influences are primarily shared or nonshared in origin. Participants were 343 postpubertal female twins (ages: 12-22 years; M = 17.61) from the Michigan State University Twin Registry. Thin-ideal internalization was assessed using the Sociocultural Attitudes toward Appearance Questionnaire-3. Twin modeling suggested significant additive genetic and nonshared environmental influences on thin-ideal internalization. Shared environmental influences were small and non-significant. Although prior research focused on psychosocial factors, genetic influences on thin-ideal internalization were significant and moderate in magnitude. Research is needed to investigate possible interplay between genetic and nonshared environmental factors in the development of thin-ideal internalization. Copyright © 2012 Wiley Periodicals, Inc.

Genetic and environmental effects on same-sex sexual behavior: a population study of twins in Sweden.

PubMed

Långström, Niklas; Rahman, Qazi; Carlström, Eva; Lichtenstein, Paul

2010-02-01

There is still uncertainty about the relative importance of genes and environments on human sexual orientation. One reason is that previous studies employed self-selected, opportunistic, or small population-based samples. We used data from a truly population-based 2005-2006 survey of all adult twins (20-47 years) in Sweden to conduct the largest twin study of same-sex sexual behavior attempted so far. We performed biometric modeling with data on any and total number of lifetime same-sex sexual partners, respectively. The analyses were conducted separately by sex. Twin resemblance was moderate for the 3,826 studied monozygotic and dizygotic same-sex twin pairs. Biometric modeling revealed that, in men, genetic effects explained .34-.39 of the variance, the shared environment .00, and the individual-specific environment .61-.66 of the variance. Corresponding estimates among women were .18-.19 for genetic factors, .16-.17 for shared environmental, and 64-.66 for unique environmental factors. Although wide confidence intervals suggest cautious interpretation, the results are consistent with moderate, primarily genetic, familial effects, and moderate to large effects of the nonshared environment (social and biological) on same-sex sexual behavior.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia.

PubMed

Bienvenu, O Joseph; Hettema, John M; Neale, Michael C; Prescott, Carol A; Kendler, Kenneth S

2007-11-01

The authors examined the extent to which two major personality dimensions (extraversion and neuroticism) index the genetic and environmental risk for three phobias (social phobia, agoraphobia, and animal phobia) in twins ascertained from a large, population-based registry. Lifetime phobias and personality traits were assessed through diagnostic interview and self-report questionnaire, respectively, in 7,800 twins from female-female, male-male, and opposite-sex pairs. Sex-limited trivariate Cholesky structural equation models were used to decompose the correlations among extraversion, neuroticism, and each phobia. In the best-fitting models, genetic correlations were moderate and negative between extraversion and both social phobia and agoraphobia, and that between extraversion and animal phobia was effectively zero. Genetic correlations were high and positive between neuroticism and both social phobia and agoraphobia, and that between neuroticism and animal phobia was moderate. All of the genetic risk factors for social phobia and agoraphobia were shared with those that influence extraversion and neuroticism; in contrast, only a small proportion of the genetic risk factors for animal phobia (16%) was shared with those that influence personality. Shared environmental experiences were not a source of correlations between personality traits and phobias, and unique environmental correlations were relatively modest. Genetic factors that influence individual variation in extraversion and neuroticism appear to account entirely for the genetic liability to social phobia and agoraphobia, but not animal phobia. These findings underline the importance of both introversion (low extraversion) and neuroticism in some psychiatric disorders.

The genetic overlap between schizophrenia and height.

PubMed

Bacanu, Silviu-Alin; Chen, Xianging; Kendler, Kenneth S

2013-12-01

Epidemiological studies suggest that height and schizophrenia risk are inversely correlated. These findings might arise because i) height and schizophrenia share genetic variants and ii) the effects of these shared variants are in opposite direction for the two traits. We use genome wide association data to empirically evaluate these hypotheses. We find that variants which impact on height and risk for schizophrenia are distributed across several genomic regions and the directions of effect vary, some consistent and others inconsistent with the direction expected from the phenotypic data. Moreover, signals that were in and not in accord with the phenotypic data aggregated in distinct biological pathways. © 2013 Elsevier B.V. All rights reserved.

Explaining individual differences in alcohol intake in adults: evidence for genetic and cultural transmission?

PubMed

van Beek, Jenny H D A; de Moor, Marleen H M; Geels, Lot M; Willemsen, Gonneke; Boomsma, Dorret I

2014-03-01

The current study aimed to describe what proportion of variation in adult alcohol intake is attributable to genetic differences among individuals and what proportion to differences in environmental experiences individuals have been exposed to. Effects of age, gender, spousal resemblance, and cultural transmission of alcohol intake from parents to offspring were taken into account. In a twin-family design, the effects of genetic and cultural transmission and shared and nonshared environment on alcohol intake were estimated with genetic structural equation models. Data originated from adult twins, their siblings, parents (n = 12,587), and spouses (n = 429) registered with the population-based Netherlands Twin Register (63.5% female; ages 18-97 years). Alcohol intake (grams per day) was higher among men than women and increased with age. Broad-sense heritability estimates were similar across sex and age (53%). Spousal resemblance was observed (r = .39) but did not significantly affect the heritability estimates. No effects of cultural transmission were detected. In total, 23% of the variation in alcohol intake was explained by additive genetic effects, 30% by dominant (nonadditive) gene action, and 47% by environmental effects that were not shared among family members. Individual differences in adult alcohol intake are explained by genetic and individual-specific environmental effects. The same genes are expressed in males and females and in younger and older participants. A substantial part of the heritability of alcohol intake is attributable to nonadditive gene action. Effects of cultural transmission that have been reported in adolescence are not present in adulthood.

Examining the etiological associations among higher-order temperament dimensions

PubMed Central

Allan, Nicholas P.; Mikolajewski, Amy J.; Lonigan, Christopher J.; Hart, Sara A.; Taylor, Jeanette

2014-01-01

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age = 10.07, SD = 1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently. PMID:24729641

Professional challenges in cancer genetic testing: who is the patient?

PubMed

Chan-Smutko, Gayun; Patel, Devanshi; Shannon, Kristen M; Ryan, Paula D

2008-03-01

In the genetic counseling setting, the health care provider can be challenged by opposing duties to members of the same family: protecting the privacy of the patient identified with a gene mutation and the ethical obligation to warn at-risk relatives. In a situation of nondisclosure between members of a family with a known disease-predisposing mutation, this type of dilemma can present in acute form for the provider who cares for different members of the family. This can hinder effective medical decision making. To minimize this effect, we recommend detailed pretest genetic counseling steps to empower the patient to communicate with their at-risk relatives their intent to pursue testing and willingness to share information. In addition, post-test counseling should reiterate the implications of a positive result for at-risk relatives and conclude with a written summary that patients can share with their family.

A national Swedish longitudinal twin-sibling study of criminal convictions from adolescence through early adulthood.

PubMed

Kendler, Kenneth S; Lönn, Sara Larsson; Maes, Hermine H; Morris, Nancy A; Lichtenstein, Paul; Sundquist, Jan; Sundquist, Kristina

2015-06-01

Prior twin and adoption studies have demonstrated the importance of both genetic and shared environmental factors in the etiology of criminal behavior (CB). However, despite substantial interest in life-course theories of CB, few genetically informative studies have examined CB in a developmental context. In 69,767 male-male twin pairs and full-sibling pairs with ≤ 2 years' difference in age, born 1958-1976 and ascertained from the Swedish Twin and Population Registries, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. We fitted a Cholesky structural model, using the OpenMx package, to CB in these pairs over three age periods: 15-19, 20-24, and 25-29. The Cholesky model had two main genetic factors. The first began at ages 15-19 and declined in importance over development. The second started at ages 20-24 and was stable over time. Only one major shared environmental factor was seen, beginning at ages 15-19. Heritability for CB declined from ages 15-29, as did shared environmental effects, although at a slower rate. Genetic risk factors for CB in males are developmentally dynamic, demonstrating both innovation and attenuation. These results are consistent with theories of adolescent-limited and life-course persistent CB subtypes. Heritability for CB did not increase over time as might be predicted from active gene-environmental correlation. However, consistent with expectation, the proportion of variability explained by shared environmental effects declined slightly as individuals aged and moved away from their original homes and neighborhoods.

Effect of ancient population structure on the degree of polymorphism shared between modern human populations and ancient hominins.

PubMed

Eriksson, Anders; Manica, Andrea

2012-08-28

Recent comparisons between anatomically modern humans and ancient genomes of other hominins have raised the tantalizing, and hotly debated, possibility of hybridization. Although several tests of hybridization have been devised, they all rely on the degree to which different modern populations share genetic polymorphisms with the ancient genomes of other hominins. However, spatial population structure is expected to generate genetic patterns similar to those that might be attributed to hybridization. To investigate this problem, we take Neanderthals as a case study, and build a spatially explicit model of the shared history of anatomically modern humans and this hominin. We show that the excess polymorphism shared between Eurasians and Neanderthals is compatible with scenarios in which no hybridization occurred, and is strongly linked to the strength of population structure in ancient populations. Thus, we recommend caution in inferring admixture from geographic patterns of shared polymorphisms, and argue that future attempts to investigate ancient hybridization between humans and other hominins should explicitly account for population structure.

Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study.

PubMed

Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Honda, Chika; Hjelmborg, Jacob vB; Möller, Sören; Ooki, Syuichi; Aaltonen, Sari; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J; Jang, Kerry L; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P; Huibregtse, Brooke M; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth Jf; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S Alexandra; Klump, Kelly L; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A; Bartels, Meike; van Beijsterveldt, Toos Cem; Craig, Jeffrey M; Saffery, Richard; Freitas, Duarte L; Maia, José Antonio; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Chong, Youngsook; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire Ma; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K Paige; Tucker-Drob, Elliot M; Öncel, Sevgi Y; Aliev, Fazil; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A; Tuvblad, Catherine; Duncan, Glen E; Buchwald, Dedra; Willemsen, Gonneke; Rasmussen, Finn; Goldberg, Jack H; Sørensen, Thorkild Ia; Boomsma, Dorret I; Kaprio, Jaakko

2016-08-01

Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity. © 2016 American Society for Nutrition.

Equality in Educational Policy and the Heritability of Educational Attainment

PubMed Central

Colodro-Conde, Lucía; Rijsdijk, Frühling; Tornero-Gómez, María J.; Sánchez-Romera, Juan F.; Ordoñana, Juan R.

2015-01-01

Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents’ education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin. PMID:26618539

Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder

PubMed Central

Hill, S. Kristian; Harris, Margret S. H.; Herbener, Ellen S.; Pavuluri, Mani; Sweeney, John A.

2008-01-01

Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed. PMID:18448479

Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds.

PubMed

Schrauwen, Isabelle; Barber, Renee M; Schatzberg, Scott J; Siniard, Ashley L; Corneveaux, Jason J; Porter, Brian F; Vernau, Karen M; Keesler, Rebekah I; Matiasek, Kaspar; Flegel, Thomas; Miller, Andrew D; Southard, Teresa; Mariani, Christopher L; Johnson, Gayle C; Huentelman, Matthew J

2014-01-01

Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

The developmental association between eating disorders symptoms and symptoms of depression and anxiety in juvenile twin girls.

PubMed

Silberg, Judy L; Bulik, Cynthia M

2005-12-01

We investigated the role of genetic and environmental factors in the developmental association among symptoms of eating disorders, depression, and anxiety syndromes in 8-13-year-old and 14-17-year-old twin girls. Multivariate genetic models were fitted to child-reported longitudinal symptom data gathered from clinical interview on 408 MZ and 198 DZ female twin pairs from the Virginia Twin Study of Adolescent Behavioural Development (VTSABD). Model-fitting revealed distinct etiological patterns underlying the association among symptoms of eating disorders, depression, overanxious disorder (OAD), and separation anxiety disorder (SAD) during the course of development: 1) a common genetic factor influencing liability to all symptoms - of early and later OAD, depression, SAD, and eating symptoms; 2) a distinct genetic factor specifically indexing liability to early eating disorders symptoms; 3) a shared environmental factor specifically influencing early depression and early eating disorders symptoms; and 4) a common environmental factor affecting liability to symptoms of later eating disorders and both early and later separation anxiety. These results suggest a pervasive genetic effect that influences liability to symptoms of over-anxiety, separation anxiety, depression, and eating disorder throughout development, a shared environmental influence on later adolescent eating problems and persistent separation anxiety, genetic influences specific to early eating disorders symptoms, and a shared environmental factor influencing symptoms of early eating and depression.

Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

PubMed

Tucker-Drob, E M; Grotzinger, A D; Briley, D A; Engelhardt, L E; Mann, F D; Patterson, M; Kirschbaum, C; Adam, E K; Church, J A; Tackett, J L; Harden, K P

2017-01-19

Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

Heritable Variation, With Little or No Maternal Effect, Accounts for Recurrence Risk to Autism Spectrum Disorder in Sweden.

PubMed

Yip, Benjamin Hon Kei; Bai, Dan; Mahjani, Behrang; Klei, Lambertus; Pawitan, Yudi; Hultman, Christina M; Grice, Dorothy E; Roeder, Kathryn; Buxbaum, Joseph D; Devlin, Bernie; Reichenberg, Abraham; Sandin, Sven

2018-04-01

Autism spectrum disorder (ASD) has both genetic and environmental origins, including potentially maternal effects. Maternal effects describe the association of one or more maternal phenotypes with liability to ASD in progeny that are independent of maternally transmitted risk alleles. While maternal effects could play an important role, consistent with association to maternal traits such as immune status, no study has estimated maternal, additive genetic, and environmental effects in ASD. Using a population-based sample consisting of all children born in Sweden from 1998 to 2007 and their relatives, we fitted statistical models to family data to estimate the variance in ASD liability originating from maternal, additive genetic, and shared environmental effects. We calculated sibling and cousin family recurrence risk ratio as a direct measure of familial, genetic, and environmental risk factors and repeated the calculations on diagnostic subgroups, specifically autistic disorder (AD) and spectrum disorder (SD), which included Asperger's syndrome and/or pervasive developmental disorder not otherwise specified. The sample consisted of 776,212 children of whom 11,231 had a diagnosis of ASD: 4554 with AD, 6677 with SD. We found support for large additive genetic contribution to liability; heritability (95% confidence interval [CI]) was estimated to 84.8% (95% CI: 73.1-87.3) for ASD, 79.6% (95% CI: 61.2-85.1) for AD, and 76.4% (95% CI: 63.0-82.5) for SD. There was modest, if any, contribution of maternal effects to liability for ASD, including subtypes AD and SD, and there was no support for shared environmental effects. These results show liability to ASD arises largely from additive genetic variation. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Association between genetic risk scoring for schizophrenia and bipolar disorder with regional subcortical volumes.

PubMed

Caseras, X; Tansey, K E; Foley, S; Linden, D

2015-12-08

Previous research has shown coincident abnormal regional brain volume in patients with schizophrenia (SCZ) and bipolar disorder (BD) compared with controls. Whether these abnormalities are genetically driven or explained by secondary effects of the disorder or environmental factors is unknown. We aimed to investigate the association between genetic risk scoring (GRS) for SCZ and BD with volume of brain areas previously shown to be different between these clinical groups and healthy controls. We obtained subcortical brain volume measures and GRS for SCZ and BD from a sample of 274 healthy volunteers (71.4% females, mean age 24.7 (s.d. 6.9)). Volume of the globus pallidus was associated with the shared GRS between SCZ and BD, and also with the independent GRS for each of these disorders. Volume of the amygdala was associated with the non-shared GRS between SCZ and BD, and with the independent GRS for BD. Our results for volume of the globus pallidus support the idea of SCZ and BD sharing a common underlying neurobiological abnormality associated with a common genetic risk for both these disorders. Results for volume of the amygdala, though, would suggest the existence of a distinct mechanism only associated with genetic risk for BD. Finally, the lack of association between genetic risk and volume of most subcortical structures suggests that the volumetric differences reported in patient-control comparisons may not be genetically driven, but a consequence of the disorder or co-occurring environmental factors.

Population Genetic Structure of the Magnificent Frigatebird Fregata magnificens (Aves, Suliformes) Breeding Colonies in the Western Atlantic Ocean

PubMed Central

Nuss, Andressa; Carlos, Caio J.; Moreno, Ignacio B.; Fagundes, Nelson J. R.

2016-01-01

The Magnificent Frigatebird Fregata magnificens has a pantropical distribution, nesting on islands along the Atlantic and Pacific coasts. In the Caribbean, there is little genetic structure among colonies; however, the genetic structure among the colonies off Brazil and its relationship with those in the Caribbean are unknown. In this study, we used mtDNA and microsatellite markers to infer population structure and evolutionary history in a sample of F. magnificens individuals collected in Brazil, Grand Connétable (French Guyana), and Barbuda. Virtually all Brazilian individuals had the same mtDNA haplotype. There was no haplotype sharing between Brazil and the Caribbean, though Grand Connétable shared haplotypes with both regions. A Bayesian clustering analysis using microsatellite data found two genetic clusters: one associated with Barbuda and the other with the Brazilian populations. Grand Connétable was more similar to Barbuda but had ancestry from both clusters, corroborating its “intermediate” position. The Caribbean and Grand Connétable populations showed higher genetic diversity and effective population size compared to the Brazilian population. Overall, our results are in good agreement with an effect of marine winds in isolating the Brazilian meta-population. PMID:26901878

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait.

PubMed

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-10-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

Delinquent peer affiliation as an etiological moderator of childhood delinquency.

PubMed

Burt, S A; Klump, K L

2013-06-01

Prior research has indicated that affiliation with delinquent peers activates genetic influences on delinquency during adolescence. However, because other studies have indicated that the socializing effects of delinquent peers vary dramatically across childhood and adolescence, it is unclear whether delinquent peer affiliation (DPA) also moderates genetic influences on delinquency during childhood. Method The current study sought to evaluate whether and how DPA moderated the etiology of delinquency in a sample of 726 child twins from the Michigan State University Twin Registry (MSUTR). The results robustly supported etiological moderation of childhood delinquency by DPA. However, this effect was observed for shared environmental, rather than genetic, influences. Shared environmental influences on delinquency were found to be several-fold larger in those with higher levels of DPA as compared to those with lower levels. This pattern of results persisted even when controlling for the overlap between delinquency and DPA. Our findings bolster prior work in suggesting that, during childhood, the association between DPA and delinquency is largely (although not solely) attributable to the effects of socialization as compared to selection. They also suggest that the process of etiological moderation is not specific to genetic influences. Latent environmental influences are also amenable to moderation by measured environmental factors.

The Effects of Both Recent and Long-Term Selection and Genetic Drift Are Readily Evident in North American Barley Breeding Populations

PubMed Central

Poets, Ana M.; Mohammadi, Mohsen; Seth, Kiran; Wang, Hongyun; Kono, Thomas J. Y.; Fang, Zhou; Muehlbauer, Gary J.; Smith, Kevin P.; Morrell, Peter L.

2015-01-01

Barley was introduced to North America ∼400 yr ago but adaptation to modern production environments is more recent. Comparisons of allele frequencies among growth habits and spike (inflorescence) types in North America indicate that significant genetic differentiation has accumulated in a relatively short evolutionary time span. Allele frequency differentiation is greatest among barley with two-row vs. six-row spikes, followed by spring vs. winter growth habit. Large changes in allele frequency among breeding programs suggest a major contribution of genetic drift and linked selection on genetic variation. Despite this, comparisons of 3613 modern North American cultivated barley breeding lines that differ for spike-type and growth habit permit the discovery of 142 single nucleotide polymorphism (SNP) outliers putatively linked to targets of selection. For example, SNPs within the Cbf4, Ppd-H1, and Vrn-H1 loci, which have previously been associated with agronomically adaptive phenotypes, are identified as outliers. Analysis of extended haplotype sharing identifies genomic regions shared within and among breeding populations, suggestive of a number of genomic regions subject to recent selection. Finally, we are able to identify recent bouts of gene flow between breeding populations that could point to the sharing of agronomically adaptive variation. These results are supported by pedigrees and breeders’ understanding of germplasm sharing. PMID:26715093

Genetic architectures of seropositive and seronegative rheumatic diseases.

PubMed

Kirino, Yohei; Remmers, Elaine F

2015-07-01

Rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and some other rheumatic diseases are genetically complex, with evidence of familial clustering, but not of Mendelian inheritance. These diseases are thought to result from contributions and interactions of multiple genetic and nongenetic risk factors, which have small effects individually. Genome-wide association studies (GWAS) of large collections of data from cases and controls have revealed many genetic factors that contribute to non-Mendelian rheumatic diseases, thus providing insights into associated molecular mechanisms. This Review summarizes methods for the identification of gene variants that influence genetically complex diseases and focuses on what we have learned about the rheumatic diseases for which GWAS have been reported. Our review of the disease-associated loci identified to date reveals greater sharing of risk loci among the groups of seropositive (diseases in which specific autoantibodies are often present) or seronegative diseases than between these two groups. The nature of the shared and discordant loci suggests important similarities and differences among these diseases.

Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

PubMed

Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

2017-06-21

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

Shared genetic aetiology of puberty timing between sexes and with health-related outcomes

PubMed Central

Day, Felix R.; Bulik-Sullivan, Brendan; Hinds, David A.; Finucane, Hilary K.; Murabito, Joanne M.; Tung, Joyce Y.; Ong, Ken K.; Perry, John R.B.

2015-01-01

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10−70) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10−12). We find five novel loci for puberty timing (P<5 × 10−8), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease. PMID:26548314

Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.

PubMed

Day, Felix R; Bulik-Sullivan, Brendan; Hinds, David A; Finucane, Hilary K; Murabito, Joanne M; Tung, Joyce Y; Ong, Ken K; Perry, John R B

2015-11-09

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10(-12)). We find five novel loci for puberty timing (P<5 × 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.

Genetic architecture of plant stress resistance: multi-trait genome-wide association mapping.

PubMed

Thoen, Manus P M; Davila Olivas, Nelson H; Kloth, Karen J; Coolen, Silvia; Huang, Ping-Ping; Aarts, Mark G M; Bac-Molenaar, Johanna A; Bakker, Jaap; Bouwmeester, Harro J; Broekgaarden, Colette; Bucher, Johan; Busscher-Lange, Jacqueline; Cheng, Xi; Fradin, Emilie F; Jongsma, Maarten A; Julkowska, Magdalena M; Keurentjes, Joost J B; Ligterink, Wilco; Pieterse, Corné M J; Ruyter-Spira, Carolien; Smant, Geert; Testerink, Christa; Usadel, Björn; van Loon, Joop J A; van Pelt, Johan A; van Schaik, Casper C; van Wees, Saskia C M; Visser, Richard G F; Voorrips, Roeland; Vosman, Ben; Vreugdenhil, Dick; Warmerdam, Sonja; Wiegers, Gerrie L; van Heerwaarden, Joost; Kruijer, Willem; van Eeuwijk, Fred A; Dicke, Marcel

2017-02-01

Plants are exposed to combinations of various biotic and abiotic stresses, but stress responses are usually investigated for single stresses only. Here, we investigated the genetic architecture underlying plant responses to 11 single stresses and several of their combinations by phenotyping 350 Arabidopsis thaliana accessions. A set of 214 000 single nucleotide polymorphisms (SNPs) was screened for marker-trait associations in genome-wide association (GWA) analyses using tailored multi-trait mixed models. Stress responses that share phytohormonal signaling pathways also share genetic architecture underlying these responses. After removing the effects of general robustness, for the 30 most significant SNPs, average quantitative trait locus (QTL) effect sizes were larger for dual stresses than for single stresses. Plants appear to deploy broad-spectrum defensive mechanisms influencing multiple traits in response to combined stresses. Association analyses identified QTLs with contrasting and with similar responses to biotic vs abiotic stresses, and below-ground vs above-ground stresses. Our approach allowed for an unprecedented comprehensive genetic analysis of how plants deal with a wide spectrum of stress conditions. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Assessing the evidence for shared genetic risks across psychiatric disorders and traits.

PubMed

Martin, Joanna; Taylor, Mark J; Lichtenstein, Paul

2017-12-04

Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

A Twin and Adoption Study of Reading Achievement: Exploration of Shared-Environmental and Gene-Environment-Interaction Effects

ERIC Educational Resources Information Center

Kirkpatrick, Robert M.; Legrand, Lisa N.; Iacono, William G.; McGue, Matt

2011-01-01

Existing behavior-genetic research implicates substantial influence of heredity and modest influence of shared environment on reading achievement and reading disability. Applying DeFries-Fulker analysis to a combined sample of twins and adoptees (N = 4886, including 266 reading-disabled probands), the present study replicates prior findings of…

Alcohol use disorder and divorce: evidence for a genetic correlation in a population-based Swedish sample.

PubMed

Salvatore, Jessica E; Larsson Lönn, Sara; Sundquist, Jan; Lichtenstein, Paul; Sundquist, Kristina; Kendler, Kenneth S

2017-04-01

We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects. We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce and the latent genetic and environmental correlations between AUD and divorce. Sweden. A total of 670 836 individuals (53% male) born 1940-1965. Life-time measures of AUD and divorce. AUD and divorce were related strongly (males: r tet  = +0.44, 95% CI = 0.43, 0.45; females r tet  = +0.37, 95% CI = 0.36, 0.38). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3%, 95% CI = 7.6, 28.5; females: 31.0%, 95% CI = 18.8, 37.1). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0%, 95% CI = 48.8, 67.9; females: 53.74%, 95% CI = 17.6, 54.5), followed by non-shared environmental factors (males: 45.0%, 95% CI = 37.5, 54.9; females: 41.6%, 95% CI = 40.3, 60.2). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0%, 95% CI = -3.0, 13.5; females: 4.75%, 95% CI = 0.0, 6.6). The AUD-divorce genetic correlations were high (males: rA = +0.76, 95% CI = 0.53, 0.90; females +0.52, 95% CI = 0.24, 0.67). The non-shared environmental correlations were modest (males: rE = +0.32, 95% CI = 0.31, 0.40; females: +0.27, 95% CI = 0.27, 0.36). Divorce and alcohol use disorder are correlated strongly in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and non-shared environmental factors. Latent genetic and non-shared environmental correlations for alcohol use disorder and divorce are high and moderate. © 2016 Society for the Study of Addiction.

The Decomposition of Shared Environmental Influences on Externalizing Syndromes in the Swedish Population: A Multivariate Study.

PubMed

Ohlsson, Henrik; Kendler, Kenneth S; Lichtenstein, Paul; Sundquist, Jan; Sundquist, Kristina

2017-08-01

Using information from Swedish population registries, we attempt to decompose the shared environment (C) into four subcomponents: close family, family, household, and community. Among pairs differing in their genetic and geographical/household relationships, we examine three externalizing syndromes: drug abuse (DA), criminal behavior (CB), and alcohol use disorders (AUD). The best-fitting common pathway model suggested that total estimates for C were higher for DA (21% for males and 18% for females) than for AUD (16% and 14%) and CB (17% and 10%). Concerning syndrome-specific influences in males, close family effects were stronger for CB and AUD, while community effects were stronger for DA. The two C components in between community experiences and close family experiences (family and household) were estimated to almost entirely derive from the common latent factor. In females, among the four components of C, the community experiences were just slightly above zero, while the C components referred to as the household effect were almost zero. The total close family experiences were similar and most important across syndromes were also divided into common and specific components. For all syndromes, for both males and females, the effects of additive genetic factors were 2-4 times the size of the total effect of the shared environment. Applying standard methods to novel relationships, we expand our understanding of how the shared environment contributes to individual differences in three externalizing syndromes.

Shared genetic variance between obesity and white matter integrity in Mexican Americans.

PubMed

Spieker, Elena A; Kochunov, Peter; Rowland, Laura M; Sprooten, Emma; Winkler, Anderson M; Olvera, Rene L; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John; Glahn, David C; Curran, Joanne E

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = -0.25), body (ρG = -0.30), and splenium (ρG = -0.26) of the corpus callosum, internal capsule (ρG = -0.29), and thalamic radiation (ρG = -0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = -0.39, p = 0.020; ρG = -0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.

Investigating cognitive transfer within the framework of music practice: genetic pleiotropy rather than causality.

PubMed

Mosing, Miriam A; Madison, Guy; Pedersen, Nancy L; Ullén, Fredrik

2016-05-01

The idea of far transfer effects in the cognitive sciences has received much attention in recent years. One domain where far transfer effects have frequently been reported is music education, with the prevailing idea that music practice entails an increase in cognitive ability (IQ). While cross-sectional studies consistently find significant associations between music practice and IQ, randomized controlled trials, however, report mixed results. An alternative to the hypothesis of cognitive transfer effects is that some underlying factors, such as shared genes, influence practice behaviour and IQ causing associations on the phenotypic level. Here we explored the hypothesis of far transfer within the framework of music practice. A co-twin control design combined with classical twin-modelling based on a sample of more than 10,500 twins was used to explore causal associations between music practice and IQ as well as underlying genetic and environmental influences. As expected, phenotypic associations were moderate (r = 0.11 and r = 0.10 for males and females, respectively). However, the relationship disappeared when controlling for genetic and shared environmental influences using the co-twin control method, indicating that a highly practiced twin did not have higher IQ than the untrained co-twin. In line with that finding, the relationship between practice and IQ was mostly due to shared genetic influences. Findings strongly suggest that associations between music practice and IQ in the general population are non-causal in nature. The implications of the present findings for research on plasticity, modularity, and transfer are discussed. © 2015 John Wiley & Sons Ltd.

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

PubMed

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2011-02-01

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

Shared genetic basis for migraine and ischemic stroke

PubMed Central

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno

2015-01-01

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857

The impact of commercialisation and genetic data sharing arrangements on public trust and the intention to participate in biobank research.

PubMed

Critchley, Christine; Nicol, Dianne; Otlowski, Margaret

2015-01-01

The necessity for biobanks to share their resources with third parties poses potential risks to public trust and the intention to participate in genetic research. We explore the effects of data sharing and the type of third-party access (public vs. private) on public trust and, in turn, the intention to participate in biobank research. An experimental design was used to assess a national sample of 1,701 Australians via a computer-assisted telephone interview. The results revealed that trust and the intention to participate significantly decreased in relation to private compared to public biobanks, and when access to third-party researchers was allowed compared to when it was not. Somewhat surprisingly, no differences were found in relation to the third party being international compared to Australian, but trust and the intention to participate were significantly eroded when private third parties were allowed access. Those with a university education were particularly distrustful of private biobanks and biobanks that allowed access, while those who were more aware of genetic databases appeared more confident with biobanks sharing with private-sector third parties. The pattern of results suggests that public awareness of the need for biobanks to share their resources widely needs to be increased to maintain public trust and support. © 2015 S. Karger AG, Basel.

A biometric latent curve analysis of memory decline in older men of the NAS-NRC twin registry.

PubMed

McArdle, John J; Plassman, Brenda L

2009-09-01

Previous research has shown cognitive abilities to have different biometric patterns of age-changes. We examined the variation in episodic memory (word recall task) for over 6,000 twin pairs who were initially aged 59-75, and were subsequently re-assessed up to three more times over 12 years. In cross-sectional analyses, variation in the number of words recalled independent of age was explained largely by non-shared influences (65-72%), with clear additive genetic influences (12-32%), and marginal shared family influences (1-18%). The longitudinal phenotypic analysis of the word recall task showed systematic linear declines over age, but several nonlinear models with more dramatic changes at later ages, improved the overall fit. A two-part spline model for the longitudinal twin data with an optimal turning point at age 74 led to: (a) a separation of non-shared environmental influences and transient measurement error (~50%); (b) strong additive genetic components of this latent curve (~44% at age 60) with increases (over 50%) up to age 74, but with no additional genetic variation after age 74; (c) the smaller influences of shared family environment (~15% at age 74) were constant over all ages; (d) non-shared effects play an important role over most of the life-span but diminish after age 74.

A multivariate twin study of early literacy in Japanese Kana

PubMed Central

Fujisawa, Keiko K.; Wadsworth, Sally J.; Kakihana, Shinichiro; Olson, Richard K.; DeFries, John C.; Byrne, Brian; Ando, Juko

2013-01-01

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children. PMID:23997545

The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.

PubMed

McAdams, T A; Rijsdijk, F V; Neiderhiser, J M; Narusyte, J; Shaw, D S; Natsuaki, M N; Spotts, E L; Ganiban, J M; Reiss, David; Leve, L D; Lichtenstein, P; Eley, T C

2015-01-01

Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.

Exploring the Relationship between Negative Urgency and Dysregulated Eating: Etiologic Associations and the Role of Negative Affect

PubMed Central

Racine, Sarah E.; Keel, Pamela K.; Burt, S. Alexandra; Sisk, Cheryl L.; Neale, Michael; Boker, Steven; Klump, Kelly L.

2013-01-01

Negative urgency (i.e., the tendency to engage in rash action in response to negative affect) has emerged as a critical personality trait contributing to individual differences in binge eating. However, studies investigating the extent to which genetic and/or environmental influences underlie the effects of negative urgency on binge eating are lacking. Moreover, it remains unclear whether negative urgency-binge eating associations are simply due to the well-established role of negative affect in the development/maintenance of binge eating. The current study addresses these gaps by examining phenotypic and etiologic associations between negative urgency, negative affect, and dysregulated eating (i.e., binge eating, emotional eating) in a sample of 222 same-sex female twin pairs from the Michigan State Twin Registry. Negative urgency was significantly associated with both dysregulated eating symptoms, even after controlling for the effects of negative affect. Genetic factors accounted for the majority (62–77%) of this phenotypic association, although a significant proportion of this genetic covariation was due to genetic influences in common with negative affect. Non-shared environmental factors accounted for a relatively smaller (23–38%) proportion of the association, but these non-shared environmental effects were independent of negative affect. Findings suggest that the presence of emotion-based rash action, combined with high levels of negative affect, may significantly increase genetic risk for dysregulated eating. PMID:23356217

Shared Genetics of Temporomandibular Disorder Pain and Neck Pain: Results of a Twin Study.

PubMed

Visscher, Corine M; Schouten, Maarten J; Ligthart, Lannie; van Houtem, Caroline Mhh; de Jongh, Ad; Boomsma, Dorret I

2018-03-06

(1) To examine the heritability of TMD pain and of neck pain; and (2) to estimate the potential overlap in genetic and environmental factors influencing TMD pain and neck pain. Data from 2,238 adult female twins who completed a survey on TMD pain and neck pain were analyzed. The total variance of TMD pain and neck pain was decomposed into variance attributable to additive genetic effects and nonshared environmental effects. Bivariate structural equation modeling was applied to estimate trait-specific and genetic effects shared between traits. The prevalence of TMD pain and neck pain was 8.6% and 46.8%, respectively, while 6.7% of the twins reported both TMD pain and neck pain. The phenotypic correlation between TMD pain and neck pain, based on a liability threshold model, was 0.43 (95% confidence interval [CI] 0.34 to 0.51). The heritability for TMD was 0.35 (0.17 to 0.51), and for neck pain was 0.33 (0.23 to 0.43). The genetic correlation between TMD pain and neck pain was 0.64 (0.35 to 1.00), and the environmental correlation was 0.32 (0.14 to 0.48). This study shows that variation in TMD pain and neck pain can in part be attributed to genes. The comorbidity between them is partly explained by genes that influence both traits and partly by the same environmental factors.

Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and Hybridization on Modern Dog Breed Development.

PubMed

Parker, Heidi G; Dreger, Dayna L; Rimbault, Maud; Davis, Brian W; Mullen, Alexandra B; Carpintero-Ramirez, Gretchen; Ostrander, Elaine A

2017-04-25

There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds. Finally, we used cladistics and haplotype sharing to show that some common traits have arisen more than once in the history of the dog. These analyses characterize the complexities of breed development, resolving longstanding questions regarding individual breed origination, the effect of migration on geographically distinct breeds, and, by inference, transfer of trait and disease alleles among dog breeds. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

PubMed

Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

2015-03-01

The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

PubMed Central

Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

2015-01-01

The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

A Biometric Latent Curve Analysis of Memory Decline in Older Men of the NAS-NRC Twin Registry

PubMed Central

McArdle, John J.; Plassman, Brenda L.

2010-01-01

Previous research has shown cognitive abilities to have different biometric patterns of age-changes. Here we examined the variation in episodic memory (Words Recalled) for over 6,000 twin pairs who were initially aged 59-75, and were subsequently re-assessed up to three more times over 12 years. In cross-sectional analyses, variation in Education was explained by strong additive genetic influences (~43%) together with shared family influences (~35%) that were independent of age. The longitudinal phenotypic analysis of the Word Recall task showed systematic linear declines over age, but with positive influences of Education and Retesting. The longitudinal biometric estimation yielded: (a) A separation of non-shared environmental influences and transient measurement error (~50%): (b) Strong additive genetic components of this latent curve (~70% at age 60) with increases over age that reach about 90% by age 90. (c) The minor influences of shared family environment (~17% at age 60) were effectively eliminated by age 75. (d) Non-shared environmental effects play an important role over most of the life-span (peak of 42% at age 70) but their relative role diminishes after age 75. PMID:19404731

Open sharing of genomic data: Who does it and why?

PubMed

Haeusermann, Tobias; Greshake, Bastian; Blasimme, Alessandro; Irdam, Darja; Richards, Martin; Vayena, Effy

2017-01-01

We explored the characteristics and motivations of people who, having obtained their genetic or genomic data from Direct-To-Consumer genetic testing (DTC-GT) companies, voluntarily decide to share them on the publicly accessible web platform openSNP. The study is the first attempt to describe open data sharing activities undertaken by individuals without institutional oversight. In the paper we provide a detailed overview of the distribution of the demographic characteristics and motivations of people engaged in genetic or genomic open data sharing. The geographical distribution of the respondents showed the USA as dominant. There was no significant gender divide, the age distribution was broad, educational background varied and respondents with and without children were equally represented. Health, even though prominent, was not the respondents' primary or only motivation to be tested. As to their motivations to openly share their data, 86.05% indicated wanting to learn about themselves as relevant, followed by contributing to the advancement of medical research (80.30%), improving the predictability of genetic testing (76.02%) and considering it fun to explore genotype and phenotype data (75.51%). Whereas most respondents were well aware of the privacy risks of their involvement in open genetic data sharing and considered the possibility of direct, personal repercussions troubling, they estimated the risk of this happening to be negligible. Our findings highlight the diversity of DTC-GT consumers who decide to openly share their data. Instead of focusing exclusively on health-related aspects of genetic testing and data sharing, our study emphasizes the importance of taking into account benefits and risks that stretch beyond the health spectrum. Our results thus lend further support to the call for a broader and multi-faceted conceptualization of genomic utility.

The mediating effect of parental neglect on adolescent and young adult anti-sociality: a longitudinal study of twins and their parents.

PubMed

Eaves, Lindon J; Prom, Elizabeth C; Silberg, Judy L

2010-07-01

The causes of correlation between parental treatment and offspring behavior are ambiguous since genetic and social factors are correlated in typical family studies. The problem is complicated by the need to characterize the effects of genes and environment on both juvenile and adult behavioral outcomes. A model is developed for the resemblance between juvenile and adult twins and their parents that allows some of these effects to be resolved. Data on childhood adversity, parental anti-social behavior, and longitudinal adult and juvenile anti-social behavior were obtained from 1,412 families of adolescent and young adult twins. A structural model is fitted that allows for the effects of genetic and social transmission of information from parents to children. Environmental effects of parents may be mediated through measured features of the home environment. Parameters were estimated by diagonal weighted least squares applied to the 33 distinct polychoric correlations between relatives and between variables within and between ages. Sub-hypotheses were tested. Results confirmed that effects of genes and environment were both highly significant. Genetic effects were large in juveniles and largely age and sex-specific. Approximately 30% of the variation due to the shared environment was due to the effect of childhood adversity. The remaining shared environmental effects are unexplained. Adversity is affected significantly by maternal anti-social behavior. The correlation between paternal ASP and adversity may be explained by antisocial fathers selecting (or creating) antisocial mothers. All significant environmental effects of parental ASP are mediated through the measure of adversity. Though transmission of ASP is both genetic and social, passive genotype-environment correlation is very small. Assortative mating for ASP has barely detectable consequence for the genetic correlation between siblings. The longitudinal study of twins and their parents makes it possible to demonstrate there is a direct causal effect of childhood adversity on child conduct disorder over and above any indirect genetic correlation.

A Primer on the Genetics of Comorbid Eating Disorders and Substance Use Disorders.

PubMed

Munn-Chernoff, Melissa A; Baker, Jessica H

2016-03-01

Eating disorders (EDs) and substance use disorders (SUDs) frequently co-occur; however, the reasons for this are unclear. We review the current literature on genetic risk for EDs and SUDs, as well as preliminary findings exploring whether these classes of disorders have overlapping genetic risk. Overall, genetic factors contribute to individual differences in liability to multiple EDs and SUDs. Although initial family studies concluded that no shared familial (which includes genetic) risk between EDs and SUDs exists, twin studies suggest a moderate proportion of shared variance is attributable to overlapping genetic factors, particularly for those EDs characterized by binge eating and/or inappropriate compensatory behaviours. No adoption or molecular genetic studies have examined shared genetic risk between these classes of disorders. Research investigating binge eating and inappropriate compensatory behaviours using emerging statistical genetic methods, as well as examining gene-environment interplay, will provide important clues into the aetiology of comorbid EDs and SUDs. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component.

PubMed

Davis, Oliver S P; Band, Gavin; Pirinen, Matti; Haworth, Claire M A; Meaburn, Emma L; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J; Hanscombe, Ken B; Trzaskowski, Maciej; Curtis, Charles J C; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Dale, Philip S; Petrill, Stephen A; Schalkwyk, Leonard S; Craig, Ian W; Lewis, Cathryn M; Price, Thomas S; Donnelly, Peter; Plomin, Robert; Spencer, Chris C A

2014-07-08

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

Community dissemination and genetic research: moving beyond results reporting.

PubMed

Trinidad, Susan Brown; Ludman, Evette J; Hopkins, Scarlett; James, Rosalina D; Hoeft, Theresa J; Kinegak, Annie; Lupie, Henry; Kinegak, Ralph; Boyer, Bert B; Burke, Wylie

2015-07-01

The community-based participatory research (CBPR) literature notes that researchers should share study results with communities. In the case of human genetic research, results may be scientifically interesting but lack clinical relevance. The goals of this study were to learn what kinds of information community members want to receive about genetic research and how such information should be conveyed. We conducted eight focus group discussions with Yup'ik Alaska Native people in southwest Alaska (N = 60) and 6 (N = 61) with members of a large health maintenance organization in Seattle, Washington. Participants wanted to receive genetic information they "could do something about" and wanted clinically actionable information to be shared with their healthcare providers; they also wanted researchers to share knowledge about other topics of importance to the community. Although Alaska Native participants were generally less familiar with western scientific terms and less interested in web-based information sources, the main findings were the same in Alaska and Seattle: participants wished for ongoing dialogue, including opportunities for informal, small-group conversations, and receiving information that had local relevance. Effective community dissemination is more than a matter of presenting study results in lay language. Community members should be involved in both defining culturally appropriate communication strategies and in determining which information should be shared. Reframing dissemination as a two-way dialogue, rather than a one-way broadcast, supports the twin aims of advancing scientific knowledge and achieving community benefit. © 2015 Wiley Periodicals, Inc.

Community Dissemination and Genetic Research: Moving Beyond Results Reporting

PubMed Central

Trinidad, Susan Brown; Ludman, Evette J.; Hopkins, Scarlett; James, Rosalina D.; Hoeft, Theresa J.; Kinegak, Annie; Lupie, Henry; Kinegak, Ralph; Boyer, Bert B.; Burke, Wylie

2015-01-01

The community-based participatory research (CBPR) literature notes that researchers should share study results with communities. In the case of human genetic research, results may be scientifically interesting but lack clinical relevance. The goals of this study were to learn what kinds of information community members want to receive about genetic research and how such information should be conveyed. We conducted 8 focus group discussions with Yup’ik Alaska Native people in southwest Alaska (N=60) and 6 (N=61) with members of a large health maintenance organization in Seattle, Washington. Participants wanted to receive genetic information they “could do something about” and wanted clinically actionable information to be shared with their healthcare providers; they also wanted researchers to share knowledge about other topics of importance to the community. Although Alaska Native participants were generally less familiar with western scientific terms and less interested in web-based information sources, the main findings were the same in Alaska and Seattle: participants wished for ongoing dialogue, including opportunities for informal, small-group conversations and receiving information that had local relevance. Effective community dissemination is more than a matter of presenting study results in lay language. Community members should be involved in both defining culturally appropriate communication strategies and in determining which information should be shared. Reframing dissemination as a two-way dialogue, rather than a one-way broadcast, supports the twin aims of advancing scientific knowledge and achieving community benefit. PMID:25900516

Effects of heritability, shared environment, and nonshared intrauterine conditions on child and adolescent BMI.

PubMed

Salsberry, Pamela J; Reagan, Patricia B

2010-09-01

Heritability studies of BMI, based upon twin samples, have identified genetic and shared environmental components of BMI, but have been largely silent about the nonshared environmental factors. Intrauterine factors have been identified as having significant long-term effects on BMI and may be a critical source of nonshared environmental influence. Extant studies based on samples of either unrelated individuals or twins cannot separate the effects of genetics, shared environments, and nonshared intrauterine conditions because the one lacks variation in the degree of relatedness and the other has insufficient variation in intrauterine conditions. This study improves upon these prior studies by using a large, sibling-based sample to examine heritability, shared environmental, and nonshared intrauterine influences on BMI during two age periods in childhood (6-8 years; 12-14 years). The primary interest was in determining the effects of the intrauterine environment on BMI as a component of the nonshared environment and in determining whether there were sex-specific differences in heritability and/or in the intrauterine factors. These were estimated using regression-based techniques introduced by DeFries and Fulker. Heritability of BMI was estimated to be 0.20-0.28 at 6-8 years and 0.46-0.61 at 12-14 years. Differences in heritability were found at 12-14 years between same-sex as compared to mixed-sex pairs. The shared environmental effect was significant at 6-8 years but insignificant at 12-14 years. Differences in birth weight were significant in all groups at 6-8 years suggesting long-term effects of the nonshared intrauterine environment; at 12-14 years, birth weight was no longer significant for girls.

Shared genetic variance between obesity and white matter integrity in Mexican Americans

PubMed Central

Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

Effect of migration patterns on maternal genetic structure: a case of Tai-Kadai migration from China to Thailand.

PubMed

Kampuansai, Jatupol; Kutanan, Wibhu; Tassi, Francesca; Kaewgahya, Massupa; Ghirotto, Silvia; Kangwanpong, Daoroong

2017-02-01

The migration of the Tai-Kadai speaking people from southern China to northern Thailand over the past hundreds of years has revealed numerous patterns that have likely been influenced by routes, purposes and periods of time. To study the effects of different migration patterns on Tai-Kadai maternal genetic structure, mitochondrial DNA hypervariable region I sequences from the Yong and the Lue people having well-documented histories in northern Thailand were analyzed. Although the Yong and Lue people were historically close relatives who shared Xishuangbanna Dai ancestors, significant genetic differences have been observed among them. The Yong people who have been known to practice mass migration have exhibited a closer genetic affinity to their Dai ancestors than have the Lue people. Genetic heterogeneity and a sudden reduced effective population size within the Lue group is likely a direct result of the circumstances of the founder effect.

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.

PubMed

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G; Terwindt, Gisela M; Sturm, Jonathan; Bis, Joshua C; Hopewell, Jemma C; Ferrari, Michel D; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I; Mitchell, Braxton D; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T; Kurth, Tobias; Ikram, M Arfan; Reiner, Alex P; Longstreth, W T; Rothwell, Peter M; Strachan, David P; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B; Davey Smith, George; van Duijn, Cornelia M; Stefansson, Kari; Worrall, Bradford B; Nyholt, Dale R; Markus, Hugh S; van den Maagdenberg, Arn M J M; Cotsapas, Chris; Zwart, John A; Palotie, Aarno; Dichgans, Martin

2015-05-26

To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO). Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. © 2015 American Academy of Neurology.

Public and Biobank Participant Attitudes toward Genetic Research Participation and Data Sharing

PubMed Central

Lemke, A.A.; Wolf, W.A.; Hebert-Beirne, J.; Smith, M.E.

2010-01-01

Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public's needs. PMID:20805700

Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

PubMed

Rutter, M; Silberg, J; O'Connor, T; Simonoff, E

1999-01-01

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.

The growth and gaps of genetic data sharing policies in the United States

PubMed Central

Arias, Jalayne J.; Pham-Kanter, Genevieve; Campbell, Eric G.

2014-01-01

The 1996 Bermuda Principles launched a new era in data sharing, reflecting a growing belief that the rapid public dissemination of research data was crucial to scientific progress in genetics. A historical review of data sharing policies in the field of genetics and genomics reflects changing scientific norms and evolving views of genomic data, particularly related to human subjects’ protections and privacy concerns. The 2013 NIH Draft Genomic Data Sharing (GDS) Policy incorporates the most significant protections and guidelines to date. The GDS Policy, however, will face difficult challenges ahead as geneticists seek to balance the very real concerns of research participants and the scientific norms that propel research forward. This article provides a novel evaluation of genetic and GDS policies’ treatment of human subjects’ protections. The article examines not only the policies, but also some of the most pertinent scientific, legal, and regulatory developments that occurred alongside data sharing policies. This historical perspective highlights the challenges that future data sharing policies, including the recently disseminated NIH GDS Draft Policy, will encounter. PMID:27774180

Shared genetic influences on negative emotionality and major depression/conduct disorder comorbidity.

PubMed

Tackett, Jennifer L; Waldman, Irwin D; Van Hulle, Carol A; Lahey, Benjamin B

2011-08-01

To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across five regions in Tennessee, with stratification by age and geographic location. Face-to-face structured interviews were conducted with the primary caregiver of a representative sample of twins. After accounting for genetic influences on negative emotionality, genetic influences on major depressive disorder/conduct disorder comorbidity were nonsignficant, but only in male twins. Specifically, 19% of the variance in the two disorders was accounted for by genetic factors shared with negative emotionality in male twins. Although the full hypothesis could not be tested in female twins, 10% to 11% of the variance in the two disorders was also accounted for by genetic factors shared with negative emotionality. Common shared environmental and nonshared environmental influences were found for major depressive disorder/conduct disorder comorbidity in male and female twins. Negative emotionality represents an important dispositional trait that may explain genetic influences on major depressive disorder/conduct disorder comorbidity, at least for boys. Models of major depressive disorder/conduct disorder comorbidity must simultaneously measure common and specific genetic and environmental factors for a full understanding of this phenomenon. Gender differences require specific research attention in dispositional factors and developmental progression. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Shared Genetic Influences on Negative Emotionality and Major Depression/Conduct Disorder Comorbidity

ERIC Educational Resources Information Center

Tackett, Jennifer L.; Waldman, Irwin D.; Van Hulle, Carol A.; Lahey, Benjamin B.

2011-01-01

Objective: To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Method: Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across…

Socioeconomic Status Moderates Genetic and Environmental Effects on the Amount of Alcohol Use

PubMed Central

Hamdi, Nayla R; Krueger, Robert F.; South, Susan C.

2015-01-01

Background Much is unknown about the relationship between socioeconomic status (SES) and alcohol use, including the means by which SES may influence risk for alcohol use. Methods Using a sample of 672 twin pairs (aged 25–74) derived from the MacArthur Foundation Survey of Midlife Development in the United States (MIDUS), the present study examined whether SES, measured by household income and educational attainment, moderates genetic and environmental influences on three indices of alcohol use: amount used, frequency of use, and problem use. Results We found significant moderation for amount of alcohol used. Specifically, genetic effects were greater in low-SES conditions, shared environmental effects (i.e., environmental effects that enhance the similarity of twins from the same families) tended to increase in high-SES conditions, and non-shared environmental effects (i.e., environmental effects that distinguish twins) tended to decrease with SES. This pattern of results was found for both income and education, and it largely replicated at a second wave of assessment spaced nine years after the first. There was virtually no evidence of moderation for either frequency of alcohol use or alcohol problems. Conclusions Our findings indicate that genetic and environmental influences on drinking amount vary as a function of the broader SES context, whereas the etiologies of other drinking phenomena are less affected by this context. Efforts to find the causes underlying the amount of alcohol used are likely to be more successful if such contextual information is taken into account. PMID:25778493

Depressive Symptoms and Heart Rate Variability: Evidence for a Shared Genetic Substrate in a Study of Twins

PubMed Central

Vaccarino, Viola; Lampert, Rachel; Bremner, J. Douglas; Lee, Forrester; Su, Shaoyong; Maisano, Carisa; Murrah, Nancy V.; Jones, Linda; Jawed, Farhan; Afzal, Nadeem; Ashraf, Ali; Goldberg, Jack

2018-01-01

Objective To clarify the relationship between depression and heart rate variability (HRV) in a sample of twins. Reduced HRV, a measure of autonomic dysfunction, has been linked to depression but many studies have inadequately controlled for familial and environmental factors. Furthermore, little is known about whether depression and HRV share common genetic pathways. Methods We performed power spectral analysis on 24-hour ambulatory electrocardiograms in 288 middle-aged male twins. Log-normalized ultra low, very low, low, high frequency, and total power were calculated. A lifetime history of major depressive disorder (MDD) was determined, using the Structured Clinical Interview for Psychiatry Disorders, and current depressive symptoms were measured with the Beck Depression Inventory. Mixed-effect regression models were used to account for intrapair variability and estimate within-pair effects at the same time controlling for potential confounders. Results Both current depressive symptoms and a history of MDD were significantly associated with lower HRV. There was a graded effect, and power in each frequency band was 29% to 36% lower in the lowest band compared with the highest BDI category. All HRV measures except high frequency remained significantly associated with current depressive symptoms in multivariable analysis, but not with lifetime history of MDD. When analyses were stratified by zygosity, a significant within-pair association between BDI score and HRV was found in the dizygotic but not in the monozygotic twins, suggesting a genetic influence on the association. Conclusions A shared, genetically influenced biological pathway underlies the association between depression and lower HRV. These two phenotypes may be the expression of a generalized neurobiological perturbation. PMID:18606724

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Genetic and environmental influences on separation anxiety disorder symptoms and their moderation by age and sex.

PubMed

Feigon, S A; Waldman, I D; Levy, F; Hay, D A

2001-09-01

We estimated genetic and environmental influences on mother-rated DSM-III-R separation anxiety disorder (SAD) symptoms in 2043 3 to 18-year-old male and female twin pairs and their siblings (348 pairs) recruited from the Australian NH&MRC Twin Registry. Using DeFries and Fulker's (1985) multiple regression analysis, we found that genetic and shared environmental influences both contributed appreciably to variation in SAD symptoms (h2 = .47, SE = .07; c2 = .21, SE = .05) and were significantly moderated by both sex and age. Genetic influences were greater for girls than boys (h2 = .50 and .14, respectively), whereas shared environmental influences were greater for boys than girls (c2 = .51 and .21, respectively). Genetic influences increased with age. whereas shared environmental influences decreased with age. Shared environmental influences were greater in magnitude for twins than for nontwin siblings (c2 = .28 versus .13, respectively). Implications of these findings for theories of the cause of separation anxiety are discussed.

Genetic variation and relationship among and within Withania species as revealed by AFLP markers.

PubMed

Negi, M S; Singh, A; Lakshmikumaran, M

2000-12-01

Withania somnifera is an important medicinal plant, and its anticancerous properties have been attributed to various classes of withanolide compounds. The objective of the present study was to investigate the inter- and intraspecific genetic variation present in 35 individuals of W. somnifera and 5 individuals of W. coagulans using AFLP (amplified fragment length polymorphism) marker technique. The information about genetic variation determined from AFLP data for 40 individuals was employed to estimate similarity matrix value based on Jaccard's coefficient. The similarity values were further used to construct a phenetic dendrogram revealing the genetic relationships. The dendrogram generated by UPGMA (unweighted pair group method of arithmetic averages) distinguished W. somnifera from W. coagulans and formed two major clusters. These two main clusters shared a similarity coefficient of 0.3, correlating with the high level of polymorphism detected. The dendrogram further separated W. somnifera into three subclasses corresponding to Kashmiri and Nagori groups and an intermediate type. The AFLP profile of Kashmiri individuals was distinct from that of the Nagori group of plants. The intermediate genotype was distinct as it shared bands with both the Kashmiri and Nagori individuals, even though it was identified as a Kashmiri morphotype. Furthermore, the intermediate type shared a similarity coefficient of 0.8 with the Kashmiri individuals. The present work revealed low levels of variation within a population though high levels of polymorphism were detected between Nagori and Kashmiri populations. The ability of AFLP markers for efficient and rapid detection of genetic variations at the species as well as intraspecific level qualifies it as an efficient tool for estimating genetic similarity in plant species and effective management of genetic resources.

Fetal Environment Is a Major Determinant of the Neonatal Blood Thyroxine Level: Results of a Large Dutch Twin Study.

PubMed

Zwaveling-Soonawala, Nitash; van Beijsterveldt, Catharina E M; Mesfum, Ertirea T; Wiedijk, Brenda; Oomen, Petra; Finken, Martijn J J; Boomsma, Dorret I; van Trotsenburg, A S Paul

2015-06-01

The interindividual variability in thyroid hormone function parameters is much larger than the intraindividual variability, suggesting an individual set point for these parameters. There is evidence to suggest that environmental factors are more important than genetic factors in the determination of this individual set point. This study aimed to quantify the effect of genetic factors and (fetal) environment on the early postnatal blood T4 concentration. This was a classical twin study comparing the resemblance of neonatal screening blood T4 concentrations in 1264 mono- and 2566 dizygotic twin pairs retrieved from the population-based Netherlands Twin Register. Maximum-likelihood estimates of variance explained by genetic and environmental influences were obtained by structural equation modeling in data from full-term and preterm twin pairs. In full-term infants, genetic factors explained 40%/31% of the variance in standardized T4 scores in boys/girls, and shared environment, 27%/22%. The remaining variance of 33%/47% was due to environmental factors not shared by twins. For preterm infants, genetic factors explained 34%/0% of the variance in boys/girls, shared environment 31%/57%, and unique environment 35%/43%. In very preterm twins, no significant contribution of genetic factors was observed. Environment explains a large proportion of the resemblance of the postnatal blood T4 concentration in twin pairs. Because we analyzed neonatal screening results, the fetal environment is the most likely candidate for these environmental influences. Genetic influences on the T4 set point diminished with declining gestational age, especially in girls. This may be due to major environmental influences such as immaturity and nonthyroidal illness in very preterm infants.

Investigating the genetic relationship between Alzheimer's disease and cancer using GWAS summary statistics.

PubMed

Feng, Yen-Chen Anne; Cho, Kelly; Lindstrom, Sara; Kraft, Peter; Cormack, Jean; Liang, Liming; Driver, Jane A

2017-10-01

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer's disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g  = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r g  = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r g  = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.

Genetic and environmental contributions to anxiety among Chinese children and adolescents--a multi-informant twin study.

PubMed

Chen, Jie; Yu, Jing; Li, Xinying; Zhang, Jianxin

2015-05-01

Child and adolescent anxiety has become a major public health concern in China, but little was known about the etiology of anxiety in Chinese children and adolescents. The present study aimed to investigate genetic and environmental influences on trait anxiety among Chinese children and adolescents. Rater, sex, and age differences on these estimates were also examined. Self-reported and parent-reported child's trait anxiety was collected from 1,104 pairs of same-sex twins aged 9-18 years. Genetic models were fitted to data from each informant to determine the genetic (A), shared (C), and non-shared environmental (E) influences on trait anxiety. The parameter estimates and 95% confidence intervals (CI) of A, C, E on self-reported trait anxiety were 50% [30%, 60%], 5% [0%, 24%], 45% [40%, 49%]. For parent-reported data, the corresponding parameter estimates were 63% [47%, 78%], 13% [1%, 28%], and 24% [22%, 27%], respectively. The heritability of anxiety was higher in girls for self-reported data, but higher in boys for parent-reported data. There was no significant age difference in genetic and environmental contributions for self-reported data, but a significant increase of heritability with age for parent-reported data. The trait anxiety in Chinese children and adolescents was highly heritable. Non-shared environmental factors also played an important role. The estimates of genetic and environmental effects differed by rater, sex and age. Our findings largely suggest the cross-cultural generalizability of the etiological model of child and adolescent anxiety. © 2014 Association for Child and Adolescent Mental Health.

Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

PubMed

Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

2012-04-01

Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours.

PubMed

Treur, Jorien L; Gibson, Mark; Taylor, Amy E; Rogers, Peter J; Munafò, Marcus R

2018-04-22

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

A Genetically Informed Cross-lagged Analysis of Autistic-Like Traits and Affective Problems in Early Childhood

PubMed Central

Micalizzi, Lauren; Ronald, Angelica; Saudino, Kimberly J.

2015-01-01

A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53% male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = .30−.53) and showed moderate stability (r = .45−.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association. PMID:26456961

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.

Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses

PubMed Central

Betjemann, Rebecca S.; Keenan, Janice M.; Olson, Richard K.; DeFries, John C.

2010-01-01

Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences. PMID:21804757

Is the psychological impact of genetic testing moderated by support and sharing of test results to family and friends?

PubMed

Lapointe, Julie; Dorval, Michel; Noguès, Catherine; Fabre, Roxane; Julian-Reynier, Claire

2013-12-01

Receiving the results of genetic tests for a breast and ovarian cancer susceptibility can be a stressful experience. Here we studied the effects of social support (SS) and the sharing of test results on the psychological impact of BRCA1/2 test result disclosure. We also compared carriers and non-carriers on sharing, SS and psychological impact. Five-hundred and twenty-two unaffected women were followed prospectively for 2 years after receiving their test results. Psychological impact was measured on the impact of event scale. Multivariate multi-level models were used, and all the analyses were stratified depending on mutation status (carriers vs non-carriers). Two weeks after receiving their BRCA1/2 results, carriers had shared their test results less frequently than non-carriers (p < 0.01). Sharing test results was not significantly associated with psychological impact. Availability of SS was significantly associated with better psychological adjustment across time among carriers (p < 0.01), but not among non-carriers. For female BRCA1/2 mutation carriers, the importance of SS should be stressed, and possible ways of enlisting people in their entourage for this purpose should be discussed in the context of clinical encounters.

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.

How do emotional restrictions affect the use of humor? A behavior genetic analysis of alexithymia and humor styles.

PubMed

Atkinson, Breanna E; Lipton, Debra; Baughman, Holly M; Schermer, Julie A; Harris, Juliette; Vernon, Philip A

2015-04-01

This article reports the first behavioral genetic study of relationships between alexithymia and four styles of humor: affiliative, self-enhancing, self-defeating, and aggressive. A total of 509 MZ pairs and 264 DZ pairs of twins completed the Toronto Alexithymia Scale-20 (TAS-20) and the Humor Styles Questionnaire (HSQ). Consistent with our predictions, alexithymia correlated negatively with affiliative and self-enhancing humor and positively with self-defeating and aggressive humor. All but one of the 16 phenotypic correlations that we report are significant at the 0.01 level. Also consistent with our predictions, the phenotypic correlations between alexithymia and humor styles were primarily attributable to correlated genetic factors and to a lesser extent to correlated non-shared environmental factors. Correlated shared environmental factors had no significant effect. Implications and limitations of this study are discussed.

Age differences in genetic and environmental influences on weight and shape concerns.

PubMed

Klump, Kelly L; Burt, S Alexandra; Spanos, Alexia; McGue, Matt; Iacono, William G; Wade, Tracey D

2010-12-01

Previous research has shown important developmental shifts ingenetic and environmental influences for disordered eating. However, little research has examined age differences for weight/shape concerns, two key components of eating disorders. The goal of this study was to investigate these age differences in preadolescent, adolescent, young adult, and mid-adult twins. Participants included 2,618 female twins (ages of 10-41 years) from three large twin registries. Shape and weight concerns were assessed with the Eating Disorders Examination Questionnaire. Genetic influences were modest in preadolescent twins, but significant from early-adolescence through middle adulthood. Shared environmental factors showed the opposite pattern, with the largest shared environmental contributions occurring in the youngest age group. Nonshared environmental effects remained relatively constant across age. Findings highlight the importance of age differences in genetic and environmental influences. Possible mechanisms include gene x environment interactions and biological changes associated with key developmental stages. © 2009 by Wiley Periodicals, Inc.

Peer Deviance, Alcohol Expectancies, and Adolescent Alcohol Use: Explaining Shared and Nonshared Environmental Effects Using an Adoptive Sibling Pair Design

PubMed Central

Samek, Diana R.; Keyes, Margaret A.; Iacono, William G.; McGue, Matt

2013-01-01

Previous research suggests adolescent alcohol use is largely influenced by environmental factors, yet little is known about the specific nature of this influence. We hypothesized that peer deviance and alcohol expectancies would be sources of environmental influence because both have been consistently and strongly correlated with adolescent alcohol use. The sample included 206 genetically related and 407 genetically unrelated sibling pairs assessed in mid-to-late adolescence. The heritability of adolescent alcohol use (e.g., frequency, quantity last 12 months) was minimal and not significantly different from zero. The associations among peer deviance, alcohol expectancies, and alcohol use were primarily due to shared environmental factors. Of special note, alcohol expectancies also significantly explained nonshared environmental influence on alcohol use. This study is one of few that have identified specific environmental variants of adolescent alcohol use while controlling for genetic influence. PMID:23644917

Peer deviance, alcohol expectancies, and adolescent alcohol use: explaining shared and nonshared environmental effects using an adoptive sibling pair design.

PubMed

Samek, Diana R; Keyes, Margaret A; Iacono, William G; McGue, Matt

2013-07-01

Previous research suggests adolescent alcohol use is largely influenced by environmental factors, yet little is known about the specific nature of this influence. We hypothesized that peer deviance and alcohol expectancies would be sources of environmental influence because both have been consistently and strongly correlated with adolescent alcohol use. The sample included 206 genetically related and 407 genetically unrelated sibling pairs assessed in mid-to-late adolescence. The heritability of adolescent alcohol use (e.g., frequency, quantity last 12 months) was minimal and not significantly different from zero. The associations among peer deviance, alcohol expectancies, and alcohol use were primarily due to shared environmental factors. Of special note, alcohol expectancies also significantly explained nonshared environmental influence on alcohol use. This study is one of few that have identified specific environmental variants of adolescent alcohol use while controlling for genetic influence.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

PubMed Central

Davis, Oliver S. P.; Band, Gavin; Pirinen, Matti; Haworth, Claire M. A.; Meaburn, Emma L.; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J.; Hanscombe, Ken B.; Trzaskowski, Maciej; Curtis, Charles J. C.; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Dale, Philip S.; Petrill, Stephen A.; Schalkwyk, Leonard S.; Craig, Ian W.; Lewis, Cathryn M.; Price, Thomas S.; Donnelly, Peter; Plomin, Robert; Spencer, Chris C. A.

2014-01-01

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve. PMID:25003214

Psychopathic personality traits in 5 year old twins: the importance of genetic and shared environmental influences.

PubMed

Tuvblad, Catherine; Fanti, Kostas A; Andershed, Henrik; Colins, Olivier F; Larsson, Henrik

2017-04-01

There is limited research on the genetic and environmental bases of psychopathic personality traits in children. In this study, psychopathic personality traits were assessed in a total of 1189 5-year-old boys and girls drawn from the Preschool Twin Study in Sweden. Psychopathic personality traits were assessed with the Child Problematic Traits Inventory, a teacher-report measure of psychopathic personality traits in children ranging from 3 to 12 years old. Univariate results showed that genetic influences accounted for 57, 25, and 74 % of the variance in the grandiose-deceitful, callous-unemotional, and impulsive-need for stimulation dimensions, while the shared environment accounted for 17, 48 and 9 % (n.s.) in grandiose-deceitful and callous-unemotional, impulsive-need for stimulation dimensions, respectively. No sex differences were found in the genetic and environmental variance components. The non-shared environment accounted for the remaining 26, 27 and 17 % of the variance, respectively. The three dimensions of psychopathic personality were moderately correlated (0.54-0.66) and these correlations were primarily mediated by genetic and shared environmental factors. In contrast to research conducted with adolescent and adult twins, we found that both genetic and shared environmental factors influenced psychopathic personality traits in early childhood. These findings indicate that etiological models of psychopathic personality traits would benefit by taking developmental stages and processes into consideration.

A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

PubMed

Kendler, K S; Maes, H H; Lönn, S L; Morris, N A; Lichtenstein, P; Sundquist, J; Sundquist, K

2015-08-01

We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics

PubMed Central

Evans, Barbara J

2014-01-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved—but still imperfect—framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics. Genet Med 16 7, 504–509. PMID:24357850

Investigating the genetic and environmental bases of biases in threat recognition and avoidance in children with anxiety problems

PubMed Central

2012-01-01

Background Adults with anxiety show biased categorization and avoidance of threats. Such biases may emerge through complex interplay between genetics and environments, occurring early in life. Research on threat biases in children has focuses on a restricted range of biases, with insufficient focus on genetic and environmental origins. Here, we explore differences between children with and without anxiety problems in under-studied areas of threat bias. We focused both on associations with anxious phenotype and the underlying gene-environmental correlates for two specific processes: the categorisation of threat faces and avoidance learning. Method Two-hundred and fifty 10-year old MZ and DZ twin pairs (500 individuals) completed tasks assessing accuracy in the labelling of threatening facial expressions and in the acquisition of avoidant responses to a card associated with a masked threatening face. To assess whether participants met criteria for an anxiety disorder, parents of twins completed a self-guided computerized version of the Development and Well-being Assessment (DAWBA). Comparison of MZ and DZ twin correlations using model-fitting were used to compute estimates of genetic, shared and non-shared environmental effects. Results Of the 500 twins assessed, 25 (5%) met diagnostic criteria for a current anxiety disorder. Children with anxiety disorders were more accurate in their ability to recognize disgust faces than those without anxiety disorders, but were commensurate on identifying other threatening face emotions (angry, fearful, sad). Children with anxiety disorders but also more strongly avoided selecting a conditioned stimulus than non-anxious children. While recognition of socially threatening faces was moderately heritable, avoidant responses were heavily influenced by the non-shared environment. Conclusion These data add to other findings on threat biases in anxious children. Specifically, we found biases in the labelling of some negative-valence faces and in the acquisition of avoidant responses. While non-shared environmental effects explained all of the variance on threat avoidance, some of this may be due to measurement error. PMID:22788754

The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits.

PubMed

Kendler, K S; Aggen, S H; Gillespie, Nathan; Neale, M C; Knudsen, G P; Krueger, R F; Czajkowski, Nikolai; Ystrom, Eivind; Reichborn-Kjennerud, T

2017-04-01

Recent work has suggested a high level of congruence between normative personality, most typically represented by the "big five" factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-5-Norwegian Brief Form (PID-5-NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-5-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-5-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI.

Combat Exposure Severity as a Moderator of Genetic and Environmental Liability to Posttraumatic Stress Disorder

PubMed Central

Wolf, Erika J.; Mitchell, Karen S.; Koenen, Karestan C.; Miller, Mark W.

2014-01-01

Background Twin studies of veterans and adults suggest that approximately 30–46% of the variance in posttraumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to examine if the effect of genetic and environmental factors that contribute to the etiology PTSD were dependent on level of combat exposure. Methods The sample was drawn from the Vietnam Era Twin Registry and included 620 male-male twin pairs who served in the U.S. Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Results Biometric modeling revealed that the effect of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Conclusions Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and other environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations. PMID:24001428

Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder.

PubMed

Wolf, E J; Mitchell, K S; Koenen, K C; Miller, M W

2014-05-01

Twin studies of veterans and adults suggest that approximately 30-46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure. The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male-male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

Shared familial risk between bulimic symptoms and alcohol involvement during adolescence.

PubMed

Baker, Jessica H; Munn-Chernoff, Melissa A; Lichtenstein, Paul; Larsson, Henrik; Maes, Hermine; Kendler, Kenneth S

2017-07-01

Twin studies show the established relation between bulimic symptoms and problematic alcohol involvement in adult females is partly due to shared familial factors, specifically shared genetic effects. However, it is unclear if similar shared etiological factors exist during adolescence or in males. We examined the familial overlap (i.e., genetic and common environmental correlations) between bulimic symptoms and various levels of alcohol involvement in 16- to 17-year-old female and male same-sex twin pairs using sex-specific biometrical twin modeling. Bulimic symptoms were assessed with the Eating Disorder Inventory-2. Alcohol involvement included alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency. Results revealed 3 distinct patterns. First, in general, phenotypic correlations indicated statistically similar associations between bulimic symptoms and alcohol involvement in girls and boys. Second, common environmental overlap was significant for the bivariate associations including having ever been intoxicated. Third, moderate genetic correlations were observed between all bulimic symptoms and alcohol involvement in girls and moderate common environmental correlations were observed in boys for the more risky/deviant levels of involvement. Similar to adults, there is familial overlap between bulimic symptoms and alcohol involvement in adolescent girls and boys. These results could inform symptom- and sex-specific, developmentally targeted prevention and intervention programs for the comorbidity between bulimic symptoms and alcohol involvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genetic testing when there is a mix of compulsory and voluntary health insurance.

PubMed

Hoel, Michael; Iversen, Tor

2002-03-01

When the insurer has access to information about test status, genetic insurance can handle the negative effects of genetic testing on insurance coverage and income distribution. Hence, efficient testing is promoted. When information about prevention and test status is private, two types of social inefficiencies may occur; genetic testing may not be done when it is socially efficient and genetic testing may be done although it is socially inefficient. The first type of inefficiency is shown to be likely for consumers with compulsory insurance only, while the second type of inefficiency is more likely for those who have supplemented the compulsory insurance with substantial voluntary insurance. This second type of inefficiency is more important the less effective prevention is. It is therefore a puzzle that many countries have imposed strict regulation on the genetic information insurers have access to. A reason may be that genetic insurance is not yet a political issue, and the advantage of shared genetic information is therefore not transparent.

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.

Beyond the big five: the Dark Triad and the supernumerary personality inventory.

PubMed

Veselka, Livia; Schermer, Julie Aitken; Vernon, Philip A

2011-04-01

The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality - results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-02-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone.

Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

PubMed

Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

2015-01-01

Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (Ps<0.05). Walkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Ps<0.05), with no attenuation accounting for shared genetic and environmental background. The association between activity and BMI is largely due to shared genetic and environmental factors, but a significant causal relationship remains accounting for shared background. Although walkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

Spatio-temporal genetic structure of Anopheles gambiae in the Northwestern Lake Victoria Basin, Uganda: implications for genetic control trials in malaria endemic regions.

PubMed

Lukindu, Martin; Bergey, Christina M; Wiltshire, Rachel M; Small, Scott T; Bourke, Brian P; Kayondo, Jonathan K; Besansky, Nora J

2018-04-16

Understanding population genetic structure in the malaria vector Anopheles gambiae (s.s.) is crucial to inform genetic control and manage insecticide resistance. Unfortunately, species characteristics such as high nucleotide diversity, large effective population size, recent range expansion, and high dispersal ability complicate the inference of genetic structure across its range in sub-Saharan Africa. The ocean, along with the Great Rift Valley, is one of the few recognized barriers to gene flow in this species, but the effect of inland lakes, which could be useful sites for initial testing of genetic control strategies, is relatively understudied. Here we examine Lake Victoria as a barrier between the Ugandan mainland and the Ssese Islands, which lie up to 60 km offshore. We use mitochondrial DNA (mtDNA) from populations sampled in 2002, 2012 and 2015, and perform Bayesian cluster analysis on mtDNA combined with microsatellite data previously generated from the same 2002 mosquito DNA samples. Hierarchical analysis of molecular variance and Bayesian clustering support significant differentiation between the mainland and lacustrine islands. In an mtDNA haplotype network constructed from this and previous data, haplotypes are shared even between localities separated by the Rift Valley, a result that more likely reflects retention of shared ancestral polymorphism than contemporary gene flow. The relative genetic isolation of An. gambiae on the Ssese Islands, their small size, level terrain and ease of access from the mainland, the relative simplicity of the vectorial system, and the prevalence of malaria, are all attributes that recommend these islands as possible sites for the testing of genetic control strategies.

What Drives the Association between Weight Conscious Peer Groups and Disordered Eating? Disentangling Genetic and Environmental Selection from Pure Socialization Effects

PubMed Central

O’Connor, Shannon M.; Burt, S. Alexandra; VanHuysse, Jessica L.; Klump, Kelly L.

2015-01-01

Previous studies suggest strong associations between exposure to weight conscious peer groups and increased levels of disordered eating. This association has been attributed to socialization effects (i.e., membership leads to disordered eating); however, selection effects (i.e., selecting into peer groups based on genetic and/or environmental predispositions toward disordered eating) could contribute to or even account for these associations. The current study was the first to use a co-twin control design to disentangle these types of selection factors from socialization effects. Participants included 610 female twins (ages 8–14) drawn from the Michigan State University Twin Registry. To comprehensively examine a range of eating pathology, several disordered eating attitudes and behaviors (e.g., body dissatisfaction, binge eating) were examined via self-report questionnaires. Questionnaires also were used to assess peer group emphasis on body weight and shape. Replicating previous results, significant individual-level associations were found between membership in weight conscious peer groups and disordered eating. However, co-twin control analyses indicated that these associations were largely due to genetic and/or shared environmental selection factors rather than pure socialization effects. Importantly, results remained unchanged when controlling for pubertal status, suggesting that effects do not vary across developmental stage. Overall, these findings question whether associations between weight conscious peer groups and disordered eating are due entirely to socialization processes. Future studies are needed to identify the specific genetic and/or shared environmental factors that may drive selection into weight conscious peer groups. PMID:27043917

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.

Genetic and Environmental Influences on Individual Differences in Attitudes Toward Homosexuality: An Australian Twin Study

PubMed Central

Shekar, Sri N.; Zietsch, Brendan P.; Eaves, Lindon J.; Bailey, J. Michael; Boomsma, Dorret I.; Martin, Nicholas G.

2008-01-01

Previous research has shown that many heterosexuals hold negative attitudes toward homosexuals and homosexuality (homophobia). Although a great deal of research has focused on the profile of homophobic individuals, this research provides little theoretical insight into the aetiology of homophobia. To examine genetic and environmental influences on variation in attitudes toward homophobia, we analysed data from 4,688 twins who completed a questionnaire concerning sexual behaviour and attitudes, including attitudes toward homosexuality. Results show that, in accordance with literature, males have significantly more negative attitudes toward homosexuality than females and non-heterosexuals are less homophobic than heterosexuals. In contrast with some earlier findings, age had no significant effect on the homophobia scores in this study. Genetic modelling showed that variation in homophobia scores could be explained by additive genetic (36%), shared environmental (18%) and unique environmental factors (46%). However, corrections based on previous findings show that the shared environmental estimate may be almost entirely accounted for as extra additive genetic variance arising from assortative mating for homophobic attitudes. The results suggest that variation in attitudes toward homosexuality is substantially inherited, and that social environmental influences are relatively minor. PMID:18347968

Gene-Environment Interplay in the Association between Pubertal Timing and Delinquency in Adolescent Girls

PubMed Central

Harden, K. Paige; Mendle, Jane

2014-01-01

Early pubertal timing places girls at elevated risk for a breadth of negative outcomes, including involvement in delinquent behavior. While previous developmental research has emphasized the unique social challenges faced by early maturing girls, this relation is complicated by genetic influences for both delinquent behavior and pubertal timing, which are seldom controlled for in existing research. The current study uses genetically informed data on 924 female-female twin and sibling pairs drawn from the National Longitudinal Study of Adolescent Health to (1) disentangle biological versus environmental mechanisms for the effects of early pubertal timing and (2) test for gene-environment interactions. Results indicate that early pubertal timing influences girls’ delinquency through a complex interplay between biological risk and environmental experiences. Genes related to earlier age at menarche and higher perceived development significantly predict increased involvement in both non-violent and violent delinquency. Moreover, after accounting for this genetic association between pubertal timing and delinquency, the impact of non-shared environmental influences on delinquency are significantly moderated by pubertal timing, such that the non-shared environment is most important among early maturing girls. This interaction effect is particularly evident for non-violent delinquency. Overall, results suggest early maturing girls are vulnerable to an interaction between genetic and environmental risks for delinquent behavior. PMID:21668078

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue.

PubMed

Narusyte, Jurgita; Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2016-02-01

Previous research indicates that liability to disability pension (DP) due to mental diagnoses is moderately influenced by genetic factors. This study investigates whether genetic contributions to the liability to DP due to mood and neurotic diagnoses overlap with the genetic influences on major depression (MD), generalized anxiety disorder (GAD), or chronic fatigue (CF). A prospective cohort study including 9,985 female twins born in Sweden 1933-1958. The presence of MD, GAD, and CF was assessed by computer-assisted telephone interviews conducted in 1998-2002. Data on DP due to mood and neurotic diagnoses were obtained from nationwide registers for the years 1998-2010. Common genetic and environmental influences on the phenotypes were estimated by applying structural equation modeling. The prevalence of MD/GAD was 30%, CF 8%, and DP due to mood and neurotic diagnoses 3% in 2010. Genetic effects on MD/GAD explained 31% of the total genetic variation in DP, whereas genetic contributions in common with CF were small and not significant. The majority of the total non-shared environmental variance in DP (85%) was explained by the factors that were unique to DP. Large proportions of genetic and non-shared environmental influences in DP due to mood and neurotic diagnoses were not explained by the contributions from MD/GAD or CF. The results suggest that the process leading to DP is complex and influenced by factors other than those related to the disorder underlying DP.

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.

PubMed

Elliott, Katherine S; Chapman, Kay; Day-Williams, Aaron; Panoutsopoulou, Kalliope; Southam, Lorraine; Lindgren, Cecilia M; Arden, Nigel; Aslam, Nadim; Birrell, Fraser; Carluke, Ian; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Rai, Ashok; Ralston, Stuart; Reed, Mike R; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, Mark; Zeggini, Eleftheria

2013-06-01

Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI. We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

PubMed Central

Elliott, Katherine S; Chapman, Kay; Day-Williams, Aaron; Panoutsopoulou, Kalliope; Southam, Lorraine; Lindgren, Cecilia M; Arden, Nigel; Aslam, Nadim; Birrell, Fraser; Carluke, Ian; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Rai, Ashok; Ralston, Stuart; Reed, Mike R; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, Mark; Zeggini, Eleftheria

2013-01-01

Objectives Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. Methods We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. Results We found significant overlap between osteoarthritis and height (p=3.3×10−5 for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10−5). As expected, this signal was attenuated when we adjusted for BMI. Conclusions We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset. PMID:22956599

Does educational attainment increase the risk of low back pain when genetics are considered? A population-based study of Spanish twins.

PubMed

Zadro, Joshua R; Shirley, Debra; Pinheiro, Marina B; Sánchez-Romera, Juan F; Pérez-Riquelme, Francisco; Ordoñana, Juan R; Ferreira, Paulo H

2017-04-01

There is limited research investigating educational attainment as a risk factor for low back pain (LBP), with the influence of gender commonly being neglected. Furthermore, genetics and early shared environment explain a substantial proportion of LBP cases and need to be controlled for when investigating risk factors for LBP. To investigate whether educational attainment affects the prevalence and risk of LBP differently in men and women while controlling for the influence of genetics and early shared environment. This is a cross-sectional and prospective twin case-control study. Adult monozygotic (MZ) and dizygotic (DZ) twins from the Murcia Twin Registry, with available data on educational attainment, formed the base sample for this study. The prevalence analysis considered twins with available data on LBP in 2013 (n=1,580). The longitudinal analysis considered twins free of LBP at baseline (2009-2011), with available data on LBP at follow-up (2013) (n=1,077). Data on the lifetime prevalence of activity limiting LBP (outcome) and educational attainment (risk factor) were self-reported. The prevalence analysis investigated the cross-sectional association between educational attainment and LBP, whereas the longitudinal analysis investigated whether educational attainment increased the risk of developing LBP. Both analyses were performed in the following sequence. First, a total sample analysis was performed on all twins (considering them as individuals), adjusting for confounding variables selected by the data. Second, to control for the influence of genetics and early shared environment, a within-pair case-control analysis (stratified by zygosity) was performed on complete twin pairs discordant for LBP (ie, one twin had LBP, whereas the co-twin did not). All analyses were stratified for gender where possible, with an interaction term determining whether gender was a significant moderator of the association between educational attainment and LBP. Women with either general secondary or university education were less likely to experience (prevalence analysis) or to develop LBP (longitudinal analysis). Educational attainment did not affect the risk of LBP in men. When controlling for the effects of genetics and early shared environment, the relationship between educational status and LBP in women was no longer statistically significant. Educational attainment affects LBP differently in men and women, with higher levels of education only decreasing the risk of developing LBP in women. After adjusting for genetics and early shared environment, the relationship between educational attainment and LBP in women disappears. This suggests that genetics and early shared environment are confounding the relationship between educational attainment and LBP in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Isocost Lines Describe the Cellular Economy of Genetic Circuits

PubMed Central

Gyorgy, Andras; Jiménez, José I.; Yazbek, John; Huang, Hsin-Ho; Chung, Hattie; Weiss, Ron; Del Vecchio, Domitilla

2015-01-01

Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings. PMID:26244745

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

PubMed Central

Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

2017-01-01

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

Etiological heterogeneity in the development of antisocial behavior: the Virginia Twin Study of Adolescent Behavioral Development and the Young Adult Follow-Up.

PubMed

Silberg, Judy L; Rutter, Michael; Tracy, Kelly; Maes, Hermine H; Eaves, Lindon

2007-08-01

Longitudinal, genetically informed, prospective data collected on a large population of male twins (n=1037) were used to examine developmental differences in the etiology of antisocial behavior. Analyses were carried out on both mother- and child-reported symptoms of conduct disorder (CD) in 10- to 17-year-old twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and self-reported antisocial behavior by the twins as young adults from the Young Adult Follow-Up (YAFU) study. The following trends were identified: (1) a single genetic factor influencing antisocial behavior beginning at age 10 through young adulthood ('life-course persistent'); (2) a shared-environmental effect beginning in adolescence ('adolescent-onset'); (3) a transient genetic effect at puberty; and (4) a genetic influence specific to adult antisocial behavior. Overall, these etiological findings are consistent with predictions from Moffitt's developmental theory of antisocial behavior. The genetic effect at puberty at ages 12-15 is also consistent with a genetically mediated influence on the timing of puberty affecting the expression of genetic differences in antisocial outcomes.

Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

PubMed Central

Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

2011-01-01

Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

PubMed

Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

2011-12-01

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Canadian Open Genetics Repository (COGR): a unified clinical genomics database as a community resource for standardising and sharing genetic interpretations.

PubMed

Lerner-Ellis, Jordan; Wang, Marina; White, Shana; Lebo, Matthew S

2015-07-01

The Canadian Open Genetics Repository is a collaborative effort for the collection, storage, sharing and robust analysis of variants reported by medical diagnostics laboratories across Canada. As clinical laboratories adopt modern genomics technologies, the need for this type of collaborative framework is increasingly important. A survey to assess existing protocols for variant classification and reporting was delivered to clinical genetics laboratories across Canada. Based on feedback from this survey, a variant assessment tool was made available to all laboratories. Each participating laboratory was provided with an instance of GeneInsight, a software featuring versioning and approval processes for variant assessments and interpretations and allowing for variant data to be shared between instances. Guidelines were established for sharing data among clinical laboratories and in the final outreach phase, data will be made readily available to patient advocacy groups for general use. The survey demonstrated the need for improved standardisation and data sharing across the country. A variant assessment template was made available to the community to aid with standardisation. Instances of the GeneInsight tool were provided to clinical diagnostic laboratories across Canada for the purpose of uploading, transferring, accessing and sharing variant data. As an ongoing endeavour and a permanent resource, the Canadian Open Genetics Repository aims to serve as a focal point for the collaboration of Canadian laboratories with other countries in the development of tools that take full advantage of laboratory data in diagnosing, managing and treating genetic diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetic and environmental contributions to the associations between intraindividual variability in reaction time and cognitive function.

PubMed

Finkel, Deborah; Pedersen, Nancy L

2014-01-01

Intraindividual variability (IIV) in reaction time has been related to cognitive decline, but questions remain about the nature of this relationship. Mean and range in movement and decision time for simple reaction time were available from 241 individuals aged 51-86 years at the fifth testing wave of the Swedish Adoption/Twin Study of Aging. Cognitive performance on four factors was also available: verbal, spatial, memory, and speed. Analyses indicated that range in reaction time could be used as an indicator of IIV. Heritability estimates were 35% for mean reaction and 20% for range in reaction. Multivariate analysis indicated that the genetic variance on the memory, speed, and spatial factors is shared with genetic variance for mean or range in reaction time. IIV shares significant genetic variance with fluid ability in late adulthood, over and above and genetic variance shared with mean reaction time.

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.

The prosocial personality and its facets: genetic and environmental architecture of mother-reported behavior of 7-year-old twins

PubMed Central

Knafo-Noam, Ariel; Uzefovsky, Florina; Israel, Salomon; Davidov, Maayan; Zahn-Waxler, Caroyln

2015-01-01

Children vary markedly in their tendency to behave prosocially, and recent research has implicated both genetic and environmental factors in this variability. Yet, little is known about the extent to which different aspects of prosociality constitute a single dimension (the prosocial personality), and to the extent they are intercorrelated, whether these aspects share their genetic and environmental origins. As part of the Longitudinal Israeli Study of Twins (LIST), mothers of 183 monozygotic (MZ) and dizygotic (DZ) 7-year-old twin pairs (51.6% male) reported regarding their children’s prosociality using questionnaires. Five prosociality facets (sharing, social concern, kindness, helping, and empathic concern) were identified. All five facets intercorrelated positively (r > 0.39) suggesting a single-factor structure to the data, consistent with the theoretical idea of a single prosociality trait. Higher MZ than DZ twin correlations indicated genetic contributions to each prosociality facet. A common-factor-common-pathway multivariate model estimated high (69%) heritability for the common prosociality factor, with the non-shared environment and error accounting for the remaining variance. For each facet, unique genetic and environmental contributions were identified as well. The results point to the presence of a broad prosociality phenotype, largely affected by genetics; whereas additional genetic and environmental factors contribute to different aspects of prosociality, such as helping and sharing. PMID:25762952

The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading Ability and General Cognitive Ability

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Thompson, Lee A.; Plomin, Robert

2009-01-01

The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic (h2 = .00 –.63) and shared (c2 = .15–.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. PMID:20157630

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study

PubMed Central

Alemany, Silvia; Rijsdijk, Frühling V.; Haworth, Claire Margaret Alison; Fañanás, Lourdes; Plomin, Robert

2013-01-01

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added asa covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors. PMID:23627958

Effects of social contact and zygosity on 21-y weight change in male twins.

PubMed

McCaffery, Jeanne M; Franz, Carol E; Jacobson, Kristen; Leahey, Tricia M; Xian, Hong; Wing, Rena R; Lyons, Michael J; Kremen, William S

2011-08-01

Recent evidence indicates that social contact is related to similarities in weight gain over time. However, no studies have examined this effect in a twin design, in which genetic and other environmental effects can also be estimated. We determined whether the frequency of social contact is associated with similarity in weight change from young adulthood (mean age: 20 y) to middle age (mean age: 41 y) in twins and quantified the percentage of variance in weight change attributable to social contact, genetic factors, and other environmental influences. Participants were 1966 monozygotic and 1529 dizygotic male twin pairs from the Vietnam-Era Twin Registry. Regression models tested whether frequency of social contact and zygosity predicted twin pair similarity in body mass index (BMI) change and weight change. Twin modeling was used to partition the percentage variance attributable to social contact, genetic, and other environmental effects. Twins gained an average of 3.99 BMI units, or 13.23 kg (29.11 lb), over 21 y. In regression models, both zygosity (P < 0.001) and degree of social contact (P < 0.02) significantly predicted twin pair similarity in BMI change. In twin modeling, social contact between twins contributed 16% of the variance in BMI change (P < 0.001), whereas genetic factors contributed 42%, with no effect of additional shared environmental factors (1%). Similar results were obtained for weight change. Frequency of social contact significantly predicted twin pair similarity in BMI and weight change over 21 y, independent of zygosity and other shared environmental influences.

A multivariate twin study of trait mindfulness, depressive symptoms, and anxiety sensitivity.

PubMed

Waszczuk, Monika A; Zavos, Helena M S; Antonova, Elena; Haworth, Claire M; Plomin, Robert; Eley, Thalia C

2015-04-01

Mindfulness-based therapies have been shown to be effective in treating depression and reducing cognitive biases. Anxiety sensitivity is one cognitive bias that may play a role in the association between mindfulness and depressive symptoms. It refers to an enhanced sensitivity toward symptoms of anxiety, with a belief that these are harmful. Currently, little is known about the mechanisms underpinning the association between mindfulness, depression, and anxiety sensitivity. The aim of this study was to examine the role of genetic and environmental factors in trait mindfulness, and its genetic and environmental overlap with depressive symptoms and anxiety sensitivity. Over 2,100 16-year-old twins from a population-based study rated their mindfulness, depressive symptoms, and anxiety sensitivity. Twin modeling analyses revealed that mindfulness is 32% heritable and 66% due to nonshared environmental factors, with no significant influence of shared environment. Genetic influences explained over half of the moderate phenotypic associations between low mindfulness, depressive symptoms, and anxiety sensitivity. About two-thirds of genetic influences and almost all nonshared environmental influences on mindfulness were independent of depression and anxiety sensitivity. This is the first study to show that both genes and environment play an important role in the etiology of mindfulness in adolescence. Future research should identify the specific environmental factors that influence trait mindfulness during development to inform targeted treatment and resilience interventions. Shared genetic liability underpinning the co-occurrence of low mindfulness, depression, and anxiety sensitivity suggests that the biological pathways shared between these traits should also be examined. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

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.

Sexual offending runs in families: A 37-year nationwide study.

PubMed

Långström, Niklas; Babchishin, Kelly M; Fazel, Seena; Lichtenstein, Paul; Frisell, Thomas

2015-04-01

Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21,566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5-5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2-4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5-2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2-2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment.

Geographical distribution of genetic diversity in Secale landrace and wild accessions.

PubMed

Hagenblad, Jenny; Oliveira, Hugo R; Forsberg, Nils E G; Leino, Matti W

2016-01-19

Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in many parts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the genetic diversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areas is largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wild and feral relatives. A total of 567 SNPs were analysed in 434 individuals from 76 accessions of wild, feral and cultivated rye. Genetic diversity was highest in cultivated rye, slightly lower in feral rye taxa and significantly lower in the wild S. strictum Presl. and S. africanum Stapf. Evaluation of effects from ascertainment bias suggests underestimation of diversity primarily in S. strictum and S. africanum. Levels of ascertainment bias, STRUCTURE and principal component analyses all supported the proposed classification of S. africanum and S. strictum as a separate species from S. cereale. S. afghanicum (Vav.) Roshev, S. ancestrale Zhuk., S. dighoricum (Vav.) Roshev, S. segetale (Zhuk.) Roshev and S. vavilovii Grossh. seemed, in contrast, to share the same gene pool as S. cereale and their genetic clustering was more dependent on geographical origin than taxonomic classification. S. vavilovii was found to be the most likely wild ancestor of cultivated rye. Among cultivated rye landraces from Europe, Asia and North Africa five geographically discrete genetic clusters were identified. These had only limited overlap with major agro-climatic zones. Slash-and-burn rye from the Finnmark area in Scandinavia formed a distinct cluster with little similarity to other landrace ryes. Regional studies of Northern and South-West Europe demonstrate different genetic distribution patterns as a result of varying cultivation intensity. With the exception of S. strictum and S. africanum different rye taxa share the majority of the genetic variation. Due to the vast sharing of genetic diversity within the S. cereale clade, ascertainment bias seems to be a lesser problem in rye than in predominantly selfing species. By exploiting within accession diversity geographic structure can be shown on a much finer scale than previously reported.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

PubMed

Evans, Barbara J

2014-07-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Body mass index gain, fast food, and physical activity: effects of shared environments over time.

PubMed

Nelson, Melissa C; Gordon-Larsen, Penny; North, Kari E; Adair, Linda S

2006-04-01

The magnitude of environmental vs. genetic effects on BMI, diet, and physical activity (PA) is widely debated. We followed a sibling cohort (where individuals shared households in childhood and adolescence) to young adulthood (when some continued sharing households and others lived apart) to examine the role of discordant environments in adult twins' divergent trends in BMI and health behaviors and to quantify the variation in BMI and behavior among all siblings that is attributable to environmental and additive genetic effects. In the National Longitudinal Study of Adolescent Health, siblings sharing households for > or =10 years as adolescents (mean age = 16.5 +/- 1.7 years; N = 5524) were followed into adulthood (mean = 22.4 +/- 1.8 years; N = 4368), self-reporting PA, sedentary behavior, and dietary characteristics. Adult BMI and adolescent z scores were derived from measured height and weight. Compared with those living together, twins living apart exhibited greater discordance in change in BMI, PA, and fast food intake from adolescence to adulthood. Adolescent household environments accounted for 8% to 10% of variation in adolescent fast food intake and sedentary behaviors and 50% of variation in adolescent overweight. Adolescent household effects on PA were substantially greater in young adulthood (accounting for 50% of variation) vs. adolescence. Young adult fast food intake was significantly affected by young adult household environment, accounting for 12% of variation. These findings highlight important environmental influences on BMI, PA, and fast food intake during the transition to adulthood. Household and physical environments play an important role in establishing long-term behavior patterns.

Creating a Social World

PubMed Central

Kendler, Kenneth S.; Jacobson, Kristen C.; Gardner, Charles O.; Gillespie, Nathan; Aggen, Steven A.; Prescott, Carol A.

2014-01-01

Context Peer-group deviance is strongly associated with externalizing behaviors. We have limited knowledge of the sources of individual differences in peer-group deviance. Objective To clarify genetic and environmental contributions to peer-group deviance in twins from mid-childhood through early adulthood. Design Retrospective assessments using a life-history calendar. Analysis by biometric growth curves. Setting General community. Participants Members of male-male pairs from the population-based Virginia Twin Registry personally interviewed in 1998–2004 (n=1802). Main Outcome Measure Self-reported peer-group deviance at ages 8 to 11, 12 to 14, 15 to 17, 18 to 21, and 22 to 25 years. Results Mean and variance of peer-group deviance increased substantially with age. Genetic effects on peer-group deviance showed a strong and steady increase over time. Family environment generally declined in importance over time. Individual-specific environmental influences on peer-group deviance levels were stable in the first 3 age periods and then increased as most twins left home. When standardized, the heritability of peer-group deviance is approximately 30% at ages 8 to 11 years and rises to approximately 50% across the last 3 time periods. Both genes and shared environment contributed to individual differences in the developmental trajectory of peer-group deviance. However, while the correlation between childhood peer-group deviance levels and the subsequent slope of peer-group deviance over time resulting from genetic factors was positive, the same relationship resulting from shared environmental factors was negative. Conclusions As male twins mature and create their own social worlds, genetic factors play an increasingly important role in their choice of peers, while shared environment becomes less influential. The individual specific environment increases in importance when individuals leave home. Individuals who have deviant peers in childhood, as a result of genetic vs shared environmental influences, have distinct developmental trajectories. Understanding the risk factors for peer-group deviance will help clarify the etiology of a range of externalizing psychopathology. PMID:17679640

Creating a social world: a developmental twin study of peer-group deviance.

PubMed

Kendler, Kenneth S; Jacobson, Kristen C; Gardner, Charles O; Gillespie, Nathan; Aggen, Steven A; Prescott, Carol A

2007-08-01

Peer-group deviance is strongly associated with externalizing behaviors. We have limited knowledge of the sources of individual differences in peer-group deviance. To clarify genetic and environmental contributions to peer-group deviance in twins from midchildhood through early adulthood. Retrospective assessments using a life-history calendar. Analysis by biometric growth curves. General community. Members of male-male pairs from the population-based Virginia Twin Registry personally interviewed in 1998-2004 (n = 1802). Self-reported peer-group deviance at ages 8 to 11, 12 to 14, 15 to 17, 18 to 21, and 22 to 25 years. Mean and variance of peer-group deviance increased substantially with age. Genetic effects on peer-group deviance showed a strong and steady increase over time. Family environment generally declined in importance over time. Individual-specific environmental influences on peer-group deviance levels were stable in the first 3 age periods and then increased as most twins left home. When standardized, the heritability of peer-group deviance is approximately 30% at ages 8 to 11 years and rises to approximately 50% across the last 3 time periods. Both genes and shared environment contributed to individual differences in the developmental trajectory of peer-group deviance. However, while the correlation between childhood peer-group deviance levels and the subsequent slope of peer-group deviance over time resulting from genetic factors was positive, the same relationship resulting from shared environmental factors was negative. As male twins mature and create their own social worlds, genetic factors play an increasingly important role in their choice of peers, while shared environment becomes less influential. The individual-specific environment increases in importance when individuals leave home. Individuals who have deviant peers in childhood, as a result of genetic vs shared environmental influences, have distinct developmental trajectories. Understanding the risk factors for peer-group deviance will help clarify the etiology of a range of externalizing psychopathology.

Neuroticism and Extraversion Share Genetic and Environmental Effects with Negative and Positive Mood Spillover in a Nationally Representative Sample

PubMed Central

Horwitz, Briana N.; Luong, Gloria; Charles, Susan T.

2008-01-01

Work-family spillover research focuses on how negative and positive moods in one life domain carry over to another domain. Domain-specific etiologies (e.g., family conflict) are often emphasized to explain spillover. Yet, strong correlations exist between spillover variables of the same emotional valence and originating from different domains, suggesting individual differences in the tendencies to prolong mood-states. The current study (N=1143 individuals) examined whether these general tendencies are associated with neuroticism and extraversion, and how genetic and environmental effects contribute to these associations. Findings revealed that neuroticism and extraversion are related to these tendencies through genetic and environmental pathways. PMID:19430588

Longitudinal Effects on Early Adolescent Language: A Twin Study

PubMed Central

DeThorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.

2016-01-01

Purpose We evaluated genetic and environmental contributions to individual differences in language skills during early adolescence, measured by both language sampling and standardized tests, and examined the extent to which these genetic and environmental effects are stable across time. Method We used structural equation modeling on latent factors to estimate additive genetic, shared environmental, and nonshared environmental effects on variance in standardized language skills (i.e., Formal Language) and productive language-sample measures (i.e., Productive Language) in a sample of 527 twins across 3 time points (mean ages 10–12 years). Results Individual differences in the Formal Language factor were influenced primarily by genetic factors at each age, whereas individual differences in the Productive Language factor were primarily due to nonshared environmental influences. For the Formal Language factor, the stability of genetic effects was high across all 3 time points. For the Productive Language factor, nonshared environmental effects showed low but statistically significant stability across adjacent time points. Conclusions The etiology of language outcomes may differ substantially depending on assessment context. In addition, the potential mechanisms for nonshared environmental influences on language development warrant further investigation. PMID:27732720

The intergenerational correlation in weight: How genetic resemblance reveals the social role of families*

PubMed Central

Martin, Molly A.

2009-01-01

According to behavioral genetics research, the intergenerational correlation in weight derives solely from shared genetic predispositions, but complete genetic determinism contradicts the scientific consensus that social and behavioral change underlies the modern obesity epidemic. To address this conundrum, this article utilizes sibling data from the National Longitudinal Study of Adolescent Health and extends structural equation sibling models to incorporate siblings’ genetic relationships to explore the role of families’ social characteristics for adolescent weight. The article is the first to demonstrate that the association between parents’ obesity and adolescent weight is both social and genetic. Furthermore, by incorporating genetic information, the shared and social origins of the correlation between inactivity and weight are better revealed. PMID:19569401

Cannabis controversies: how genetics can inform the study of comorbidity.

PubMed

Agrawal, Arpana; Lynskey, Michael T

2014-03-01

To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. Selective review. Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. © 2014 Society for the Study of Addiction.

Cannabis Controversies: How genetics can inform the study of comorbidity

PubMed Central

Agrawal, Arpana; Lynskey, Michael T.

2014-01-01

Aims To review three key and controversial comorbidities of cannabis use – other illicit drug use, psychosis and depression as well as suicide, from a genetically informed perspective. Design Selective review. Results Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Conclusions Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. PMID:24438181

Aging Trajectories in Different Body Systems Share Common Environmental Etiology: The Healthy Aging Twin Study (HATS).

PubMed

Moayyeri, Alireza; Hart, Deborah J; Snieder, Harold; Hammond, Christopher J; Spector, Timothy D; Steves, Claire J

2016-02-01

Little is known about the extent to which aging trajectories of different body systems share common sources of variance. We here present a large twin study investigating the trajectories of change in five systems: cardiovascular, respiratory, skeletal, morphometric, and metabolic. Longitudinal clinical data were collected on 3,508 female twins in the TwinsUK registry (complete pairs:740 monozygotic (MZ), 986 dizygotic (DZ), mean age at entry 48.9 ± 10.4, range 18-75 years; mean follow-up 10.2 ± 2.8 years, range 4-17.8 years). Panel data on multiple age-related variables were used to estimate biological ages for each individual at each time point, in linear mixed effects models. A weighted average approach was used to combine variables within predefined body system groups. Aging trajectories for each system in each individual were then constructed using linear modeling. Multivariate structural equation modeling of these aging trajectories showed low genetic effects (heritability), ranging from 2% in metabolic aging to 22% in cardiovascular aging. However, we found a significant effect of shared environmental factors on the variations in aging trajectories in cardiovascular (54%), skeletal (34%), morphometric (53%), and metabolic systems (53%). The remainder was due to environmental factors unique to each individual plus error. Multivariate Cholesky decomposition showed that among aging trajectories for various body systems there were significant and substantial correlations between the unique environmental latent factors as well as shared environmental factors. However, there was no evidence for a single common factor for aging. This study, the first of its kind in aging, suggests that diverse organ systems share non-genetic sources of variance for aging trajectories. Confirmatory studies are needed using population-based twin cohorts and alternative methods of handling missing data.

Genetic studies of human neuropathic pain conditions: a review

PubMed Central

Zorina-Lichtenwalter, Katerina; Parisien, Marc; Diatchenko, Luda

2018-01-01

Abstract Numerous studies have shown associations between genetic variants and neuropathic pain disorders. Rare monogenic disorders are caused by mutations of substantial effect size in a single gene, whereas common disorders are likely to have a contribution from multiple genetic variants of mild effect size, representing different biological pathways. In this review, we survey the reported genetic contributors to neuropathic pain and submit them for validation in a 150,000-participant sample of the U.K. Biobank cohort. Successfully replicated association with a neuropathic pain construct for 2 variants in IL10 underscores the importance of neuroimmune interactions, whereas genome-wide significant association with low back pain (P = 1.3e-8) and false discovery rate 5% significant associations with hip, knee, and neck pain for variant rs7734804 upstream of the MAT2B gene provide evidence of shared contributing mechanisms to overlapping pain conditions at the molecular genetic level. PMID:29240606

Genetic and environmental influences on residential location in the U.S

PubMed Central

Duncan, Glen E.; Dansie, Elizabeth J.; Strachan, Eric; Munsell, Melissa; Huang, Ruizhu; Moudon, Anne Vernez; Goldberg, Jack; Buchwald, Dedra

2012-01-01

We used a classical twin design and measures of neighborhood walkability and social deprivation, using each twin’s street address, to examine genetic and environmental influences on the residential location of 1,389 same-sex pairs from a U.S. community-based twin registry. Within-pair correlations and structural equation models estimated these influences on walkability among younger (ages 18–24.9) and older (ages 25+) twins. Adjusting for social deprivation, walkability of residential location was primarily influenced by common environment with lesser contributions of unique environment and genetic factors among younger twins, while unique environment most strongly influenced walkability, with small genetic and common environment effects, among older twins. Thus, minimal variance in walkability was explained by shared genetic effects in younger and older twins, and confirms the importance of environmental factors in walkability of residential locations. PMID:22377617

Back-neck pain and symptoms of anxiety and depression: a population-based twin study.

PubMed

Reichborn-Kjennerud, T; Stoltenberg, C; Tambs, K; Roysamb, E; Kringlen, E; Torgersen, S; Harris, J R

2002-08-01

Clinical and epidemiological studies have shown an association between anxiety and depression and pain in the back and neck. The nature of this relationship is not clear. This study aimed to investigate the extent to which common genetic and environmental aetiological factors contribute to the covariance between symptoms of anxiety and depression and back-neck pain. Measures of back-neck pain and symptoms of anxiety and depression were part of a self-report questionnaire sent in 1992 to twins born in Norway between 1967 and 1974 (3996 pairs). Structural equation modelling was applied to determine to what extent back-neck pain and symptoms of anxiety and depression share genetic and environmental liability factors. The phenotypic correlation between symptoms of anxiety and depression and back-neck pain was 0.31. Individual differences in both anxiety and depression and back-neck pain were best accounted for by additive genetic and individual environmental factors. Heritability estimates were 0.53 and 0.30 respectively. For back-neck pain, however, a model specifying only shared- and individual environmental effects could not be rejected. Bivariate analyses revealed that the correlation between back-neck pain and symptoms of anxiety and depression was best explained by additive genetic and individual environmental factors. Genetic factors affecting both phenotypes accounted for 60% of the covariation. There were no significant sex differences. The results support previous findings of a moderate association between back-neck pain and symptoms of anxiety and depression, and suggest that this association is primarily due to common genetic effects.

Social Science Methods for Twins Data: Integrating Causality, Endowments and Heritability

PubMed Central

Kohler, Hans-Peter; Behrman, Jere R.; Schnittker, Jason

2011-01-01

Twins have been extensively used in economics, sociology and behavioral genetics to investigate the role of genetic endowments on a broad range of social, demographic and economic outcomes. However, the focus in these literatures has been distinct: the economic literature has been primarily concerned with the need to control for unobserved endowments—including as an important subset, genetic endowments—in analyses that attempt to establish the impact of one variable, often schooling, on a variety of economic, demographic and health outcomes. Behavioral genetic analyses have mostly been concerned with decomposing the variation in the outcomes of interest into genetic, shared environmental and non-shared environmental components, with recent multivariate analyses investigating the contributions of genes and the environment to the correlation and causation between variables. Despite the fact that twins studies and the recognition of the role of endowments are central to both of these literatures, they have mostly evolved independently. In this paper we develop formally the relationship between the economic and behavioral genetic approaches to the analyses of twins, and we develop an integrative approach that combines the identification of causal effects, which dominates the economic literature, with the decomposition of variances and covariances into genetic and environmental factors that is the primary goal of behavioral genetic approaches. We apply this integrative ACE-β approach to an illustrative investigation of the impact of schooling on several demographic outcomes such as fertility and nuptiality and health. PMID:21845929

Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

PubMed

Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

2016-05-13

Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

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.

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

Hedrick, P.W.

A number of studies indicates that there is a high sharing of HLA antigens in couples having recurrent spontaneous abortions. The genetic hypothesis to explain this phenomenon suggests that this fetal loss results from homozygosity of recessive lethal or deleterius alleles in gametic disequilibrium with HLA antigens. Theory predicting the lethality rate is derived when antigens are shared at one, two or three loci, given the disequilibrium is absolute. In addition, the effects of partial disequilibrium, inbreeding, and segregation distortion on the lethal proportion are examined.

A search for imprinted quantitative trait loci (QTLs) for birth weight

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

Pandya, A.; Llewellyn, B.; Schieken, R.

1994-09-01

Previous studies have generally provided strong evidence that maternal effects are a much more important determinant of birth weight than the genes of the fetus. In the past, these findings have been interpreted as reflecting a genetically determined maternal constraint on fetal growth. However, the recognition that the expression of a gene can be influenced by its parental origin has provided an alternative explanation for apparent maternal effects. In the mouse, a growing number of imprinted genes have been identified which can profoundly influence birth weight or body size including IGF-1, IGF-2, and their respective receptor loci. To determine whethermore » any of the loci are QTLs for body size in man, we have used parental typing data to classify dizygotic twins according to their identity by descent (IBD) for polymorphic markers at or near the candidate loci. The contrast between the correlations of DZ pairs sharing both alleles IBD and no alleles IBD can provide evidence for a candidate gene effect while the contrast between twins sharing one maternal or one paternal allele IBD can provide evidence for any effect of imprinting that may exist at the locus. Finally, the inclusion of data on MZ twins in an overall analysis permits the resolution of the imprinting and marker gene effects from other sources of genetic and environmental variation. We have applied this model to birth weight data on 181 pairs of twins who were classified according to their allele sharing at the IGF-1 locus. In keeping with other observations, the data show no evidence that the IGF-1 locus is imprinted in man. Although our results are consistent with the possibility that this locus may account for 15-20% of the genetic variation, the apparent effect is not statistically significant. Partitioned twin analysis appears to be a useful method for detecting the effects of specific candidate gene on continuously distributed traits.« less

The Role of Adolescent Nutrition and Physical Activity in the Prediction of Verbal Intelligence during Early Adulthood: A Genetically Informed Analysis of Twin Pairs

PubMed Central

Jackson, Dylan B.; Beaver, Kevin M.

2015-01-01

A large body of research has revealed that nutrition and physical activity influence brain functioning at various stages of the life course. Nevertheless, very few studies have explored whether diet and exercise influence verbal intelligence as youth transition from adolescence into young adulthood. Even fewer studies have explored the link between these health behaviors and verbal intelligence while accounting for genetic and environmental factors that are shared between siblings. Employing data from the National Longitudinal Study of Adolescent Health, the current study uses a sample of same-sex twin pairs to test whether youth who engage in poorer fitness and nutritional practices are significantly more likely to exhibit reduced verbal intelligence during young adulthood. The results suggests that, independent of the effects of genetic and shared environmental factors, a number of nutritional and exercise factors during adolescence influence verbal intelligence during adulthood. Limitations are noted and suggestions for future research are outlined. PMID:25568969

Origins of individual differences in anxiety proneness: a twin/adoption study of the anxiety-related scales from the Karolinska Scales of Personality (KSP).

PubMed

Gustavsson, J P; Pedersen, N L; Asberg, M; Schalling, D

1996-06-01

The genetic and environmental origins of individual differences in scores on the anxiety-proneness scales from the Karolinska Scales of Personality were explored using a twin/adoption study design in a sample consisting of 15 monozygotic twin pairs reared apart, and 26 monozygotic and 29 dizygotic twin pairs reared together. The results showed that genetic factors accounted for individual differences in scores on the psychasthenia and somatic anxiety scales. The genetic determinants were not specific to each scale, but were common to both scales. Shared-rearing environmental determinants were important for individual differences in lack of assertiveness and psychic anxiety, and were common to both scales. Individual differences in muscular tension were found to be attributable to the effects of correlated environments. The most important factor explaining individual differences for all scales was the non-shared environment component. The evidence for an aetiologically heterogeneous anxiety-proneness construct emphasizes the appropriateness of a multi-dimensional approach to anxiety proneness.

Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

USGS Publications Warehouse

Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

2001-01-01

We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors

PubMed Central

Thornton, Laura M.; Welch, Elisabeth; Munn-Chernoff, Melissa A.; Lichtenstein, Paul; Bulik, Cynthia M.

2015-01-01

We evaluated the extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA). Participants were 6,899 women from the Swedish Twin study of Adults Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the co-expression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. PMID:26916469

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors.

PubMed

Thornton, Laura M; Welch, Elisabeth; Munn-Chernoff, Melissa A; Lichtenstein, Paul; Bulik, Cynthia M

2016-10-01

The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. © 2016 The American Association of Suicidology.

Sharing the benefits of genetic resources: from biodiversity to human genetics.

PubMed

Schroeder, Doris; Lasén-Díaz, Carolina

2006-12-01

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.

Analysis of shared heritability in common disorders of the brain.

PubMed

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K; Walters, Raymond K; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N; Reitz, Christiane; Goate, Alison M; Huentelman, Matthew J; Kamboh, M Ilyas; Larson, Eric B; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A; Farrer, Lindsay A; Barnes, Lisa L; Beach, Thomas G; Demirci, F Yesim; Head, Elizabeth; Hulette, Christine M; Jicha, Gregory A; Kauwe, John S K; Kaye, Jeffrey A; Leverenz, James B; Levey, Allan I; Lieberman, Andrew P; Pankratz, Vernon S; Poon, Wayne W; Quinn, Joseph F; Saykin, Andrew J; Schneider, Lon S; Smith, Amanda G; Sonnen, Joshua A; Stern, Robert A; Van Deerlin, Vivianna M; Van Eldik, Linda J; Harold, Denise; Russo, Giancarlo; Rubinsztein, David C; Bayer, Anthony; Tsolaki, Magda; Proitsi, Petra; Fox, Nick C; Hampel, Harald; Owen, Michael J; Mead, Simon; Passmore, Peter; Morgan, Kevin; Nöthen, Markus M; Rossor, Martin; Lupton, Michelle K; Hoffmann, Per; Kornhuber, Johannes; Lawlor, Brian; McQuillin, Andrew; Al-Chalabi, Ammar; Bis, Joshua C; Ruiz, Agustin; Boada, Mercè; Seshadri, Sudha; Beiser, Alexa; Rice, Kenneth; van der Lee, Sven J; De Jager, Philip L; Geschwind, Daniel H; Riemenschneider, Matthias; Riedel-Heller, Steffi; Rotter, Jerome I; Ransmayr, Gerhard; Hyman, Bradley T; Cruchaga, Carlos; Alegret, Montserrat; Winsvold, Bendik; Palta, Priit; Farh, Kai-How; Cuenca-Leon, Ester; Furlotte, Nicholas; Kurth, Tobias; Ligthart, Lannie; Terwindt, Gisela M; Freilinger, Tobias; Ran, Caroline; Gordon, Scott D; Borck, Guntram; Adams, Hieab H H; Lehtimäki, Terho; Wedenoja, Juho; Buring, Julie E; Schürks, Markus; Hrafnsdottir, Maria; Hottenga, Jouke-Jan; Penninx, Brenda; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Hämäläinen, Eija; Huang, Hailiang; Huang, Jie; Sandor, Cynthia; Webber, Caleb; Muller-Myhsok, Bertram; Schreiber, Stefan; Salomaa, Veikko; Loehrer, Elizabeth; Göbel, Hartmut; Macaya, Alfons; Pozo-Rosich, Patricia; Hansen, Thomas; Werge, Thomas; Kaprio, Jaakko; Metspalu, Andres; Kubisch, Christian; Ferrari, Michel D; Belin, Andrea C; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret; Eriksson, Nicholas; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Avbersek, Andreja; Baum, Larry; Berkovic, Samuel; Bradfield, Jonathan; Buono, Russell; Catarino, Claudia B; Cossette, Patrick; De Jonghe, Peter; Depondt, Chantal; Dlugos, Dennis; Ferraro, Thomas N; French, Jacqueline; Hjalgrim, Helle; Jamnadas-Khoda, Jennifer; Kälviäinen, Reetta; Kunz, Wolfram S; Lerche, Holger; Leu, Costin; Lindhout, Dick; Lo, Warren; Lowenstein, Daniel; McCormack, Mark; Møller, Rikke S; Molloy, Anne; Ng, Ping-Wing; Oliver, Karen; Privitera, Michael; Radtke, Rodney; Ruppert, Ann-Kathrin; Sander, Thomas; Schachter, Steven; Schankin, Christoph; Scheffer, Ingrid; Schoch, Susanne; Sisodiya, Sanjay M; Smith, Philip; Sperling, Michael; Striano, Pasquale; Surges, Rainer; Thomas, G Neil; Visscher, Frank; Whelan, Christopher D; Zara, Federico; Heinzen, Erin L; Marson, Anthony; Becker, Felicitas; Stroink, Hans; Zimprich, Fritz; Gasser, Thomas; Gibbs, Raphael; Heutink, Peter; Martinez, Maria; Morris, Huw R; Sharma, Manu; Ryten, Mina; Mok, Kin Y; Pulit, Sara; Bevan, Steve; Holliday, Elizabeth; Attia, John; Battey, Thomas; Boncoraglio, Giorgio; Thijs, Vincent; Chen, Wei-Min; Mitchell, Braxton; Rothwell, Peter; Sharma, Pankaj; Sudlow, Cathie; Vicente, Astrid; Markus, Hugh; Kourkoulis, Christina; Pera, Joana; Raffeld, Miriam; Silliman, Scott; Boraska Perica, Vesna; Thornton, Laura M; Huckins, Laura M; William Rayner, N; Lewis, Cathryn M; Gratacos, Monica; Rybakowski, Filip; Keski-Rahkonen, Anna; Raevuori, Anu; Hudson, James I; Reichborn-Kjennerud, Ted; Monteleone, Palmiero; Karwautz, Andreas; Mannik, Katrin; Baker, Jessica H; O'Toole, Julie K; Trace, Sara E; Davis, Oliver S P; Helder, Sietske G; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Danner, Unna N; van Elburg, Annemarie A; Clementi, Maurizio; Forzan, Monica; Docampo, Elisa; Lissowska, Jolanta; Hauser, Joanna; Tortorella, Alfonso; Maj, Mario; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Papezova, Hana; Yilmaz, Zeynep; Wagner, Gudrun; Cohen-Woods, Sarah; Herms, Stefan; Julià, Antonio; Rabionet, Raquel; Dick, Danielle M; Ripatti, Samuli; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri J; Steen, Vidar M; Pinto, Dalila; Scherer, Stephen W; Aschauer, Harald; Schosser, Alexandra; Alfredsson, Lars; Padyukov, Leonid; Halmi, Katherine A; Mitchell, James; Strober, Michael; Bergen, Andrew W; Kaye, Walter; Szatkiewicz, Jin Peng; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miguel; Hervas, Amaia; Arranz, Maria Jesús; Haavik, Jan; Zayats, Tetyana; Johansson, Stefan; Williams, Nigel; Dempfle, Astrid; Rothenberger, Aribert; Kuntsi, Jonna; Oades, Robert D; Banaschewski, Tobias; Franke, Barbara; Buitelaar, Jan K; Arias Vasquez, Alejandro; Doyle, Alysa E; Reif, Andreas; Lesch, Klaus-Peter; Freitag, Christine; Rivero, Olga; Palmason, Haukur; Romanos, Marcel; Langley, Kate; Rietschel, Marcella; Witt, Stephanie H; Dalsgaard, Soeren; Børglum, Anders D; Waldman, Irwin; Wilmot, Beth; Molly, Nikolas; Bau, Claiton H D; Crosbie, Jennifer; Schachar, Russell; Loo, Sandra K; McGough, James J; Grevet, Eugenio H; Medland, Sarah E; Robinson, Elise; Weiss, Lauren A; Bacchelli, Elena; Bailey, Anthony; Bal, Vanessa; Battaglia, Agatino; Betancur, Catalina; Bolton, Patrick; Cantor, Rita; Celestino-Soper, Patrícia; Dawson, Geraldine; De Rubeis, Silvia; Duque, Frederico; Green, Andrew; Klauck, Sabine M; Leboyer, Marion; Levitt, Pat; Maestrini, Elena; Mane, Shrikant; De-Luca, Daniel Moreno-; Parr, Jeremy; Regan, Regina; Reichenberg, Abraham; Sandin, Sven; Vorstman, Jacob; Wassink, Thomas; Wijsman, Ellen; Cook, Edwin; Santangelo, Susan; Delorme, Richard; Rogé, Bernadette; Magalhaes, Tiago; Arking, Dan; Schulze, Thomas G; Thompson, Robert C; Strohmaier, Jana; Matthews, Keith; Melle, Ingrid; Morris, Derek; Blackwood, Douglas; McIntosh, Andrew; Bergen, Sarah E; Schalling, Martin; Jamain, Stéphane; Maaser, Anna; Fischer, Sascha B; Reinbold, Céline S; Fullerton, Janice M; Guzman-Parra, José; Mayoral, Fermin; Schofield, Peter R; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska; Schumacher, Johannes; Bauer, Michael; Mitchell, Philip B; Gershon, Elliot S; Rice, John; Potash, James B; Zandi, Peter P; Craddock, Nick; Ferrier, I Nicol; Alda, Martin; Rouleau, Guy A; Turecki, Gustavo; Ophoff, Roel; Pato, Carlos; Anjorin, Adebayo; Stahl, Eli; Leber, Markus; Czerski, Piotr M; Cruceanu, Cristiana; Jones, Ian R; Posthuma, Danielle; Andlauer, Till F M; Forstner, Andreas J; Streit, Fabian; Baune, Bernhard T; Air, Tracy; Sinnamon, Grant; Wray, Naomi R; MacIntyre, Donald J; Porteous, David; Homuth, Georg; Rivera, Margarita; Grove, Jakob; Middeldorp, Christel M; Hickie, Ian; Pergadia, Michele; Mehta, Divya; Smit, Johannes H; Jansen, Rick; de Geus, Eco; Dunn, Erin; Li, Qingqin S; Nauck, Matthias; Schoevers, Robert A; Beekman, Aartjan Tf; Knowles, James A; Viktorin, Alexander; Arnold, Paul; Barr, Cathy L; Bedoya-Berrio, Gabriel; Bienvenu, O Joseph; Brentani, Helena; Burton, Christie; Camarena, Beatriz; Cappi, Carolina; Cath, Danielle; Cavallini, Maria; Cusi, Daniele; Darrow, Sabrina; Denys, Damiaan; Derks, Eske M; Dietrich, Andrea; Fernandez, Thomas; Figee, Martijn; Freimer, Nelson; Gerber, Gloria; Grados, Marco; Greenberg, Erica; Hanna, Gregory L; Hartmann, Andreas; Hirschtritt, Matthew E; Hoekstra, Pieter J; Huang, Alden; Huyser, Chaim; Illmann, Cornelia; Jenike, Michael; Kuperman, Samuel; Leventhal, Bennett; Lochner, Christine; Lyon, Gholson J; Macciardi, Fabio; Madruga-Garrido, Marcos; Malaty, Irene A; Maras, Athanasios; McGrath, Lauren; Miguel, Eurípedes C; Mir, Pablo; Nestadt, Gerald; Nicolini, Humberto; Okun, Michael S; Pakstis, Andrew; Paschou, Peristera; Piacentini, John; Pittenger, Christopher; Plessen, Kerstin; Ramensky, Vasily; Ramos, Eliana M; Reus, Victor; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Roessner, Veit; Rosário, Maria; Samuels, Jack F; Sandor, Paul; Stein, Dan J; Tsetsos, Fotis; Van Nieuwerburgh, Filip; Weatherall, Sarah; Wendland, Jens R; Wolanczyk, Tomasz; Worbe, Yulia; Zai, Gwyneth; Goes, Fernando S; McLaughlin, Nicole; Nestadt, Paul S; Grabe, Hans-Jorgen; Depienne, Christel; Konkashbaev, Anuar; Lanzagorta, Nuria; Valencia-Duarte, Ana; Bramon, Elvira; Buccola, Nancy; Cahn, Wiepke; Cairns, Murray; Chong, Siow A; Cohen, David; Crespo-Facorro, Benedicto; Crowley, James; Davidson, Michael; DeLisi, Lynn; Dinan, Timothy; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Haan, Lieuwe; Hougaard, David; Karachanak-Yankova, Sena; Khrunin, Andrey; Klovins, Janis; Kučinskas, Vaidutis; Lee Chee Keong, Jimmy; Limborska, Svetlana; Loughland, Carmel; Lönnqvist, Jouko; Maher, Brion; Mattheisen, Manuel; McDonald, Colm; Murphy, Kieran C; Nenadic, Igor; van Os, Jim; Pantelis, Christos; Pato, Michele; Petryshen, Tracey; Quested, Digby; Roussos, Panos; Sanders, Alan R; Schall, Ulrich; Schwab, Sibylle G; Sim, Kang; So, Hon-Cheong; Stögmann, Elisabeth; Subramaniam, Mythily; Toncheva, Draga; Waddington, John; Walters, James; Weiser, Mark; Cheng, Wei; Cloninger, Robert; Curtis, David; Gejman, Pablo V; Henskens, Frans; Mattingsdal, Morten; Oh, Sang-Yun; Scott, Rodney; Webb, Bradley; Breen, Gerome; Churchhouse, Claire; Bulik, Cynthia M; Daly, Mark; Dichgans, Martin; Faraone, Stephen V; Guerreiro, Rita; Holmans, Peter; Kendler, Kenneth S; Koeleman, Bobby; Mathews, Carol A; Price, Alkes; Scharf, Jeremiah; Sklar, Pamela; Williams, Julie; Wood, Nicholas W; Cotsapas, Chris; Palotie, Aarno; Smoller, Jordan W; Sullivan, Patrick; Rosand, Jonathan; Corvin, Aiden; Neale, Benjamin M

2018-06-22

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

PubMed Central

Fesel, Constantin; Barreto, Marta; Ferreira, Ricardo C.; Costa, Nuno; Venda, Lara L.; Pereira, Clara; Carvalho, Claudia; Morães-Fontes, Maria Francisca; Ferreira, Carlos M.; Vasconcelos, Carlos; Viana, João F.; Santos, Eugenia; Martins, Berta; Demengeot, Jocelyne; Vicente, Astrid M.

2012-01-01

In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4+CD25bright T-cells that were regularly 70–90% Foxp3+. We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects. PMID:22479496

Invited review: Inbreeding in the genomics era: Inbreeding, inbreeding depression, and management of genomic variability.

PubMed

Howard, Jeremy T; Pryce, Jennie E; Baes, Christine; Maltecca, Christian

2017-08-01

Traditionally, pedigree-based relationship coefficients have been used to manage the inbreeding and degree of inbreeding depression that exists within a population. The widespread incorporation of genomic information in dairy cattle genetic evaluations allows for the opportunity to develop and implement methods to manage populations at the genomic level. As a result, the realized proportion of the genome that 2 individuals share can be more accurately estimated instead of using pedigree information to estimate the expected proportion of shared alleles. Furthermore, genomic information allows genome-wide relationship or inbreeding estimates to be augmented to characterize relationships for specific regions of the genome. Region-specific stretches can be used to more effectively manage areas of low genetic diversity or areas that, when homozygous, result in reduced performance across economically important traits. The use of region-specific metrics should allow breeders to more precisely manage the trade-off between the genetic value of the progeny and undesirable side effects associated with inbreeding. Methods tailored toward more effectively identifying regions affected by inbreeding and their associated use to manage the genome at the herd level, however, still need to be developed. We have reviewed topics related to inbreeding, measures of relatedness, genetic diversity and methods to manage populations at the genomic level, and we discuss future challenges related to managing populations through implementing genomic methods at the herd and population levels. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Altruistic Behavior among Twins : Willingness to Fight and Self-Sacrifice for Their Closest Relatives.

PubMed

Tornero, Encarnación; Sánchez-Romera, Juan F; Morosoli, José J; Vázquez, Alexandra; Gómez, Ángel; Ordoñana, Juan R

2018-03-01

According to kin selection theory, indirect reproductive advantages may induce individuals to care for others with whom they share genes by common descent, and the amount of care, including self-sacrifice, will increase with the proportion of genes shared. Twins represent a natural situation in which this hypothesis can be tested. Twin pairs experience the same early environment because they were born and raised at the same time and in the same family but their genetic relatedness differs depending on zygosity. We compared the degree of willingness to fight and sacrifice for the co-twin among monozygotic (MZ) and dizygotic (DZ) pairs in a sample of 1443 same-sex and opposite-sex twins. We also analyzed the effect of the subject's gender and that of the co-twin on those altruistic behaviors. Results partly supported the postulated explanation. MZ twins (who share nearly their entire genome) were significantly more likely than DZ twins (who on average share half of their segregating genes) to self-sacrifice for their co-twins, but zygosity did not affect willingness to fight for him/her. The genders of the subject and of the co-twin, not genetic relatedness, were the best predictors of aggressive altruistic intentions.

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

PubMed Central

2012-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer represent two diseases that share a strong risk factor in smoking, and COPD increases risk of lung cancer even after adjusting for the effects of smoking. These diseases not only occur jointly within an individual but also there is evidence of shared occurrence within families. Understanding the genetic contributions to these diseases, both individually and jointly, is needed to identify the highest risk group for screening and targeted prevention, as well as aiding in the development of targeted treatments. The chromosomal regions that have been identified as being associated either jointly or independently with lung cancer, COPD, nicotine addiction, and lung function are presented. Studies jointly measuring genetic variation in lung cancer and COPD have been limited by the lack of detailed COPD diagnosis and severity data in lung cancer populations, the lack of lung cancer–specific phenotypes (histology and tumor markers) in COPD populations, and the lack of inclusion of minorities. African Americans, who smoke fewer cigarettes per day and have different linkage disequilibrium and disease patterns than whites, and Asians, also with different patterns of exposure to lung carcinogens and linkage patterns, will provide invaluable information to better understand shared and independent genetic contributions to lung cancer and COPD to more fully define the highest risk group of individuals who will most benefit from screening and to develop molecular signatures to aid in targeted treatment and prevention efforts. PMID:22550237

Shared Genetic Contributions to Anxiety Disorders and Pathological Gambling in a Male Population

PubMed Central

Giddens, Justine L.; Xian, Hong; Scherrer, Jeffrey F.; Eisen, Seth A.; Potenza, Marc N.

2013-01-01

Background Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Method Data from the Vietnam Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). Results While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (ra =0.53). In contrast, substantial correlations were observed between both the genetic (ra=0.34) and unique environmental (re =0.31) contributions to PG and PD. Limitations Results may be limited to middle aged males. Conclusions The existence of shared genetic contributions between PG and both GAD and PD suggest that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women, adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. PMID:21481943

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

PubMed

Giddens, Justine L; Xian, Hong; Scherrer, Jeffrey F; Eisen, Seth A; Potenza, Marc N

2011-08-01

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. Results may be limited to middle aged males. The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. Copyright © 2011. Published by Elsevier B.V.

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed Central

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-01-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone. PMID:12618417

The Genetic Liability to Disability Retirement: A 30-Year Follow-Up Study of 24,000 Finnish Twins

PubMed Central

Harkonmäki, Karoliina; Silventoinen, Karri; Levälahti, Esko; Pitkäniemi, Janne; Huunan-Seppälä, Antti; Klaukka, Timo; Koskenvuo, Markku; Kaprio, Jaakko

2008-01-01

Background No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders. Methods The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement. Results The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71). Conclusions A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation. PMID:18923678

Genetic and Environmental Contributions to Behavioral Stability and Change in Children 6-36 months of Age Using Louisville Twin Study Data.

PubMed

Davis, Deborah Winders; Finkel, Deborah; Turkheimer, Eric; Dickens, William

2015-11-01

The Infant Behavior Record (IBR) from the Bayley Scales of Infant Development has been used to study behavioral development since the 1960s. Matheny (1983) examined behavioral development at 6, 12, 18, and 24 months from the Louisville Twin Study (LTS). The extracted temperament scales included Task Orientation, Affect-Extraversion, and Activity. He concluded that monozygotic twins were more similar than same-sex dizygotic twins on these dimensions. Since this seminal work was published, a larger LTS sample and more advanced analytical methods are available. In the current analyses, Choleksy decomposition was applied to behavioral data (n = 1231) from twins 6-36 months. Different patterns of genetic continuity vs genetic innovations were identified for each IBR scale. Single common genetic and shared environmental factors explained cross-age twin similarity in the Activity scale. Multiple shared environmental factors and a single genetic factor coming on line at age 18 months contributed to Affect-Extraversion. A single shared environmental factor and multiple genetic factors explained cross-age twin similarity in Task Orientation.

Are children's activity levels determined by their genes or environment? A systematic review of twin studies.

PubMed

Fisher, Abigail; Smith, Lee; van Jaarsveld, Cornelia H M; Sawyer, Alexia; Wardle, Jane

2015-01-01

The importance of physical activity to paediatric health warrants investigation into its determinants. Objective measurement allows a robust examination of genetic and environmental influences on physical activity. To systematically review the evidence on the extent of genetic and environmental influence on children's objectively-measured activity levels from twin studies. Medline, EMBASE, PsycINFO, Health and Psychosocial Instruments and all Ovid Databases. Search terms: "accelerometer" OR "actometer" OR "motion sensor" OR "heart rate monitor" OR "physical activity energy expenditure" AND "twin". Limited to Human, English language and children (0-18 years). Seven sets of analyses were included in the review. Six analyses examined children's daily-life activity and found that the shared environment had a strong influence on activity levels (weighted mean 60%), with a smaller contribution from genetic factors (weighted mean 21%). Two analyses examined short-term, self-directed activity in a standard environment and found a smaller shared environment effect (weighted mean 25%) and a larger genetic estimate (weighted mean 45%). Although genetic influences may be expressed when children have brief opportunities for autonomous activity, activity levels in daily-life are predominantly explained by environmental factors. Future research should aim to identify key environmental drivers of childhood activity.

Education Modifies Genetic and Environmental Influences on BMI

PubMed Central

Johnson, Wendy; Kyvik, Kirsten Ohm; Skytthe, Axel; Deary, Ian J.; Sørensen, Thorkild I. A.

2011-01-01

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity. PMID:21283825

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

PubMed

Hassan, Nik Norliza Nik; Plazzer, John-Paul; Smith, Timothy D; Halim-Fikri, Hashim; Macrae, Finlay; Zubaidi, A A L; Zilfalil, Bin Alwi

2016-02-26

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world.

Genetic and Environmental Influences on Depressive Symptoms in Chinese Adolescents

PubMed Central

Chen, Jie; Li, Xinying; Natsuaki, Misaki N.; Leve, Leslie D.; Harold, Gordon T.

2016-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1181 twin pairs residing in Beijing, China (ages 11 to 19 years). Child- and parent-versions of the Children’s Depression Inventory (CDI) were used to measure adolescents’ depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50%, 5%, and 45% of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51%, 18%, and 31% of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents. PMID:24311200

Genetic and environmental influences on depressive symptoms in Chinese adolescents.

PubMed

Chen, Jie; Li, Xinying; Natsuaki, Misaki N; Leve, Leslie D; Harold, Gordon T

2014-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1,181 twin pairs residing in Beijing, China (ages 11-19 years). Child- and parent-versions of the children's depression inventory were used to measure adolescents' depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50, 5, and 45 % of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51, 18, and 31 % of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents.

Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment

PubMed Central

Le Hellard, Stéphanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco; Hugdahl, Kenneth; Espeseth, Thomas; Steen, Vidar M.; Melle, Ingrid; Desikan, Rahul; Schork, Andrew J.; Thompson, Wesley K.; Dale, Anders M.; Djurovic, Srdjan

2017-01-01

Abstract There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a “proxy phenotype” for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion (“College,” n = 95 427), and years of education (“EduYears,” n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ. PMID:27338279

Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment.

PubMed

Le Hellard, Stéphanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco; Hugdahl, Kenneth; Espeseth, Thomas; Steen, Vidar M; Melle, Ingrid; Desikan, Rahul; Schork, Andrew J; Thompson, Wesley K; Dale, Anders M; Djurovic, Srdjan; Andreassen, Ole A

2017-05-01

There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a "proxy phenotype" for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion ("College," n = 95 427), and years of education ("EduYears," n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ. © 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.

Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor

PubMed Central

Walter, Stefan; Glymour, M. Maria; Koenen, Karestan; Liang, Liming; Tchetgen Tchetgen, Eric J; Cornelis, Marilyn; Chang, Shun-Chiao; Rewak, Marissa; Rimm, Eric; Kawachi, Ichiro; Kubzansky, Laura D.

2015-01-01

Background Obesity and anxiety are often linked but the direction of effects is not clear. Methods Using genetic instrumental variable (IV) analyses in a sample of 5911 female participants from the Nurses´ Health Study (NHS, initiated in 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated in 1986), we aim to determine whether obesity increases symptoms of phobic anxiety. FTO, MC4R, and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms that significantly predict body mass index (BMI), were used as instrumental variables. “Functional” GRS corresponding with specific biological pathways that shape BMI (adipogenesis, appetite, and cardio-pulmonary), were considered. Phobic anxiety as measured by the Crown Crisp Experimental Index (CCI) in 2004 in NHS and 2000 in HPFS was the main outcome. Results In observational analysis, a one unit higher BMI was associated with higher phobic anxiety symptoms (women NHS: beta=0.05; 95% Confidence Interval (CI): 0.030 – 0.068 and men, HPFS, beta = 0.04; 95% CI: 0.016 – 0.071). IV analyses showed that BMI instrumented by FTO was associated with higher phobic anxiety symptoms (p = 0.005) but BMI instrumented by GRS was not (p=0.256). Functional GRS scores showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms. Conclusions Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, i.e., that obesity and phobic anxiety may share common genetic determinants. PMID:25065638

Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor.

PubMed

Walter, S; Glymour, M M; Koenen, K; Liang, L; Tchetgen Tchetgen, E J; Cornelis, M; Chang, S-C; Rewak, M; Rimm, E; Kawachi, I; Kubzansky, L D

2015-01-01

Obesity and anxiety are often linked but the direction of effects is not clear. Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). 'Functional' GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS. In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030-0.068; men: β = 0.04, 95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms. Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

Etiological heterogeneity in the development of antisocial behavior: the Virginia Twin Study of Adolescent Behavioral Development and the Young Adult Follow-Up

PubMed Central

SILBERG, JUDY L.; RUTTER, MICHAEL; TRACY, KELLY; MAES, HERMINE H.; EAVES, LINDON

2014-01-01

Background Longitudinal, genetically informed, prospective data collected on a large population of male twins (n = 1037) were used to examine developmental differences in the etiology of antisocial behavior. Method Analyses were carried out on both mother- and child-reported symptoms of conduct disorder (CD) in 10- to 17-year-old twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and self-reported antisocial behavior by the twins as young adults from the Young Adult Follow-Up (YAFU) study. Results The following trends were identified: (1) a single genetic factor influencing antisocial behavior beginning at age 10 through young adulthood (‘life-course persistent’); (2) a shared-environmental effect beginning in adolescence (‘adolescent-onset’); (3) a transient genetic effect at puberty; and (4) a genetic influence specific to adult antisocial behavior. Conclusions Overall, these etiological findings are consistent with predictions from Moffitt’s developmental theory of antisocial behavior. The genetic effect at puberty at ages 12–15 is also consistent with a genetically mediated influence on the timing of puberty affecting the expression of genetic differences in antisocial outcomes. PMID:17376258

Admixture into and within sub-Saharan Africa.

PubMed

Busby, George Bj; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris Ca

2016-06-21

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

PubMed

Fennema-Notestine, Christine; McEvoy, Linda K; Notestine, Randy; Panizzon, Matthew S; Yau, Wai-Ying Wendy; Franz, Carol E; Lyons, Michael J; Eyler, Lisa T; Neale, Michael C; Xian, Hong; McKenzie, Ruth E; Kremen, William S

2016-01-01

White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E- ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age ( t  = 1.9, p  = 0.05) and hypertension ( t  = 2.9, p  = 0.004), but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled ( t  = 3.0, p  = 0.003) and normotensive ( t  = 4.0, p  = 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a 2  = 0.81) and shared some genetic influences with systolic blood pressure (r A  = 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery.

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.

Adaptive responses and disruptive effects: how major wildfire influences kinship-based social interactions in a forest marsupial.

PubMed

Banks, Sam C; Blyton, Michaela D J; Blair, David; McBurney, Lachlan; Lindenmayer, David B

2012-02-01

Environmental disturbance is predicted to play a key role in the evolution of animal social behaviour. This is because disturbance affects key factors underlying social systems, such as demography, resource availability and genetic structure. However, because natural disturbances are unpredictable there is little information on their effects on social behaviour in wild populations. Here, we investigated how a major wildfire affected cooperation (sharing of hollow trees) by a hollow-dependent marsupial. We based two alternative social predictions on the impacts of fire on population density, genetic structure and resources. We predicted an adaptive social response from previous work showing that kin selection in den-sharing develops as competition for den resources increases. Thus, kin selection should occur in burnt areas because the fire caused loss of the majority of hollow-bearing trees, but no detectable mortality. Alternatively, fire may have a disruptive social effect, whereby postfire home range-shifts 'neutralize' fine-scale genetic structure, thereby removing opportunities for kin selection between neighbours. Both predictions occurred: the disruptive social effect in burnt habitat and the adaptive social response in adjacent unburnt habitat. The latter followed a massive demographic influx to unburnt 'refuge' habitat that increased competition for dens, leading to a density-related kin selection response. Our results show remarkable short-term plasticity of animal social behaviour and demonstrate how the social effects of disturbance extend into undisturbed habitat owing to landscape-scale demographic shifts. We predicted long-term changes in kinship-based cooperative behaviour resulting from the genetic and resource impacts of forecast changes to fire regimes in these forests. © 2011 Blackwell Publishing Ltd.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

PubMed

Routledge, Kylie M; Burton, Karen L O; Williams, Leanne M; Harris, Anthony; Schofield, Peter R; Clark, C Richard; Gatt, Justine M

2016-10-30

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic Overlap Between Schizophrenia and Volumes of Hippocampus, Putamen, and Intracranial Volume Indicates Shared Molecular Genetic Mechanisms.

PubMed

Smeland, Olav B; Wang, Yunpeng; Frei, Oleksandr; Li, Wen; Hibar, Derrek P; Franke, Barbara; Bettella, Francesco; Witoelar, Aree; Djurovic, Srdjan; Chen, Chi-Hua; Thompson, Paul M; Dale, Anders M; Andreassen, Ole A

2018-06-06

Schizophrenia (SCZ) is associated with differences in subcortical brain volumes and intracranial volume (ICV). However, little is known about the underlying etiology of these brain alterations. Here, we explored whether brain structure volumes and SCZ share genetic risk factors. Using conditional false discovery rate (FDR) analysis, we integrated genome-wide association study (GWAS) data on SCZ (n = 82315) and GWAS data on 7 subcortical brain volumes and ICV (n = 11840). By conditioning the FDR on overlapping associations, this statistical approach increases power to discover genetic loci. To assess the credibility of our approach, we studied the identified loci in larger GWAS samples on ICV (n = 26577) and hippocampal volume (n = 26814). We observed polygenic overlap between SCZ and volumes of hippocampus, putamen, and ICV. Based on conjunctional FDR < 0.05, we identified 2 loci shared between SCZ and ICV implicating genes FOXO3 (rs10457180) and ITIH4 (rs4687658), 2 loci shared between SCZ and hippocampal volume implicating SLC4A10 (rs4664442) and SPATS2L (rs1653290), and 2 loci shared between SCZ and volume of putamen implicating DCC (rs4632195) and DLG2 (rs11233632). The loci shared between SCZ and hippocampal volume or ICV had not reached significance in the primary GWAS on brain phenotypes. Proving our point of increased power, 2 loci did reach genome-wide significance with ICV (rs10457180) and hippocampal volume (rs4664442) in the larger GWAS. Three of the 6 identified loci are novel for SCZ. Altogether, the findings provide new insights into the relationship between SCZ and brain structure volumes, suggesting that their genetic architectures are not independent.

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

PubMed Central

Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry. PMID:28622394

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

PubMed

Heraclides, Alexandros; Bashiardes, Evy; Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis; Cariolou, Marios A

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7-8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.

Isocost Lines Describe the Cellular Economy of Genetic Circuits.

PubMed

Gyorgy, Andras; Jiménez, José I; Yazbek, John; Huang, Hsin-Ho; Chung, Hattie; Weiss, Ron; Del Vecchio, Domitilla

2015-08-04

Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Breast Cancer

MedlinePlus

... a genetic counselor, who can review your family health history. A genetic counselor can also discuss the benefits, risks and limitations of genetic testing to assist you with shared decision-making. Risk ...

Accounting for female space sharing in St. Kilda Soay sheep (Ovis aries) results in little change in heritability estimates.

PubMed

Regan, C E; Pilkington, J G; Bérénos, C; Pemberton, J M; Smiseth, P T; Wilson, A J

2017-01-01

When estimating heritability in free-living populations, it is common practice to account for common environment effects, because of their potential to generate phenotypic covariance among relatives thereby biasing heritability estimates. In quantitative genetic studies of natural populations, however, philopatry, which results in relatives being clustered in space, is rarely accounted for. The two studies that have been carried out so far suggest absolute declines in heritability estimates of up to 43% when accounting for space sharing by relatives. However, due to methodological limitations these estimates may not be representative. We used data from the St. Kilda Soay sheep population to estimate heritabilities with and without accounting for space sharing for five traits for which there is evidence for additive genetic variance (birthweight, birth date, lamb August weight, and female post-mortem jaw and metacarpal length). We accounted for space sharing by related females by separately incorporating spatial autocorrelation, and a home range similarity matrix. Although these terms accounted for up to 18% of the variance in these traits, heritability estimates were only reduced by up to 7%. Our results suggest that the bias caused by not accounting for space sharing may be lower than previously thought. This suggests that philopatry does not inevitably lead to a large bias if space sharing by relatives is not accounted for. We hope our work stimulates researchers to model shared space when relatives in their study population share space, as doing so will enable us to better understand when bias may be of particular concern. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

I think, therefore I am: a twin study of attributional style in adolescents.

PubMed

Lau, Jennifer Y F; Rijsdijk, Frühling; Eley, Thalia C

2006-07-01

Parenting factors may be important to the development of attributional style in adolescence, which in turn relates to depression symptoms. These relationships have mainly been considered in terms of social risk mechanisms, and little is known about the role of genetic influences. Self-reported measures of attributional style, depression symptoms and parental disciplinary styles were administered to over 1300 adolescent twin and sibling pairs. Model-fitting techniques were used to examine the role of genetic and environmental influences. Moderate genetic influences on attributional style were demonstrated, and furthermore, its association with depression reflected considerable genetic effects. Familial factors were implicated in the association between attributional style and punitive parenting, although genetic from shared environmental causes could not be distinguished. Our results demonstrate that attributional style is influenced by genetic, as well as social factors. Implications for aetiological pathways integrating cognitive, genetic and social factors on adolescent depression are discussed.

Shared genetic determinants of axial length and height in children: the Guangzhou twin eye study.

PubMed

Zhang, Jian; Hur, Yoon-Mi; Huang, Wenyong; Ding, Xiaohu; Feng, Ke; He, Mingguang

2011-01-01

To describe the association between axial length (AL) and height and to estimate the extent to which shared genetic or environmental factors influence this covariance. Study participants were recruited from the Guangzhou Twin Registry. Axial length was measured using partial coherence laser interferometry. Height was measured with the participants standing without shoes. We computed twin pairwise correlations and cross-twin cross-trait correlations between AL and height for monozygotic and dizygotic twins and performed model-fitting analyses using a multivariate Cholesky model. The right eye was arbitrarily selected to represent AL of participants. Five hundred sixty-five twin pairs (359 monozygotic and 206 dizygotic) aged 7 to 15 years were available for analysis. Phenotypic correlation between AL and height was 0.46 but decreased to 0.19 after adjusting for age, sex, and age × sex interaction. Bivariate Cholesky model-fitting analyses revealed that 89% of phenotypic correlation was due to shared genetic factors and 11% was due to shared random environmental factors, which includes measurement error. Covariance of AL and height is largely attributable to shared genes. Given that AL is a key determinant of myopia, further work is needed to confirm gene sharing between myopia and stature.

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

PubMed

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development.

PubMed

Stergiakouli, Evie; Davey Smith, George; Martin, Joanna; Skuse, David H; Viechtbauer, Wolfgang; Ring, Susan M; Ronald, Angelica; Evans, David E; Fisher, Simon E; Thapar, Anita; St Pourcain, Beate

2017-01-01

Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) symptoms have been reported. Cross-trait genetic relationships are, however, subject to dynamic changes during development. We investigated the continuity of genetic overlap between ASD and ADHD symptoms in a general population sample during childhood and adolescence. We also studied uni- and cross-dimensional trait-disorder links with respect to genetic ADHD and ASD risk. Social-communication difficulties ( N  ≤ 5551, Social and Communication Disorders Checklist, SCDC) and combined hyperactive-impulsive/inattentive ADHD symptoms ( N  ≤ 5678, Strengths and Difficulties Questionnaire, SDQ-ADHD) were repeatedly measured in a UK birth cohort (ALSPAC, age 7 to 17 years). Genome-wide summary statistics on clinical ASD (5305 cases; 5305 pseudo-controls) and ADHD (4163 cases; 12,040 controls/pseudo-controls) were available from the Psychiatric Genomics Consortium. Genetic trait variances and genetic overlap between phenotypes were estimated using genome-wide data. In the general population, genetic influences for SCDC and SDQ-ADHD scores were shared throughout development. Genetic correlations across traits reached a similar strength and magnitude (cross-trait r g  ≤ 1, p min   =  3 × 10 -4 ) as those between repeated measures of the same trait (within-trait r g  ≤ 0.94, p min   =  7 × 10 -4 ). Shared genetic influences between traits, especially during later adolescence, may implicate variants in K-RAS signalling upregulated genes ( p -meta = 6.4 × 10 -4 ). Uni-dimensionally, each population-based trait mapped to the expected behavioural continuum: risk-increasing alleles for clinical ADHD were persistently associated with SDQ-ADHD scores throughout development (marginal regression R 2  = 0.084%). An age-specific genetic overlap between clinical ASD and social-communication difficulties during childhood was also shown, as per previous reports. Cross-dimensionally, however, neither SCDC nor SDQ-ADHD scores were linked to genetic risk for disorder. In the general population, genetic aetiologies between social-communication difficulties and ADHD symptoms are shared throughout child and adolescent development and may implicate similar biological pathways that co-vary during development. Within both the ASD and the ADHD dimension, population-based traits are also linked to clinical disorder, although much larger clinical discovery samples are required to reliably detect cross-dimensional trait-disorder relationships.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

PubMed

Israeli, Moshe; Kristt, Don; Nardi, Yuval; Klein, Tirza

2014-05-01

Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry.

PubMed

Palmer, Rohan H C; McGeary, John E; Heath, Andrew C; Keller, Matthew C; Brick, Leslie A; Knopik, Valerie S

2015-12-01

Genetic studies of alcohol dependence (AD) have identified several candidate loci and genes, but most observed effects are small and difficult to reproduce. A plausible explanation for inconsistent findings may be a violation of the assumption that genetic factors contributing to each of the seven DSM-IV criteria point to a single underlying dimension of risk. Given that recent twin studies suggest that the genetic architecture of AD is complex and probably involves multiple discrete genetic factors, the current study employed common single nucleotide polymorphisms in two multivariate genetic models to examine the assumption that the genetic risk underlying DSM-IV AD is unitary. AD symptoms and genome-wide single nucleotide polymorphism (SNP) data from 2596 individuals of European descent from the Study of Addiction: Genetics and Environment were analyzed using genomic-relatedness-matrix restricted maximum likelihood. DSM-IV AD symptom covariance was described using two multivariate genetic factor models. Common SNPs explained 30% (standard error=0.136, P=0.012) of the variance in AD diagnosis. Additive genetic effects varied across AD symptoms. The common pathway model approach suggested that symptoms could be described by a single latent variable that had a SNP heritability of 31% (0.130, P=0.008). Similarly, the exploratory genetic factor model approach suggested that the genetic variance/covariance across symptoms could be represented by a single genetic factor that accounted for at least 60% of the genetic variance in any one symptom. Additive genetic effects on DSM-IV alcohol dependence criteria overlap. The assumption of common genetic effects across alcohol dependence symptoms appears to be a valid assumption. © 2015 Society for the Study of Addiction.

Cognitive performance and BMI in childhood: Shared genetic influences between reaction time but not response inhibition

USDA-ARS?s Scientific Manuscript database

The aim of this work is to understand whether shared genetic influences can explain the associationbetween obesity and cognitive performance, including slower and more variable reaction times(RTs) and worse response inhibition. RT on a four-choice RT task and the go/no-go task, and commission errors...

Preschool Drawing and School Mathematics: The Nature of the Association

PubMed Central

Malanchini, M.; Tosto, M.G.; Garfield, V.; Czerwik, A.; Dirik, A.; Arden, R.; Malykh, S.

2016-01-01

The study examined the aetiology of individual differences in early drawing and of its longitudinal association with school mathematics. Participants (N = 14,760), members of the Twins Early Development Study, were assessed on their ability to draw a human figure, including number of features, symmetry and proportionality. Human figure drawing was moderately stable across six months (average r = .40). Individual differences in drawing at age 4½ were influenced by genetic (.21), shared environmental (.30) and non-shared environmental (.49) factors. Drawing was related to later (age 12) mathematical ability (average r = .24). This association was explained by genetic and shared environmental factors that also influenced general intelligence. Some genetic factors, unrelated to intelligence, also contributed to individual differences in drawing. PMID:27079561

Genetic counseling

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

Genetic Counseling

MedlinePlus

... Testing Evaluating Genomic Tests Epidemiology Pathogen Genomics Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

Exploring links among imitation, mental development, and temperament

PubMed Central

Fenstermacher, Susan K.; Saudino, Kimberly J.

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children’s imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique. PMID:27840593

Exploring links among imitation, mental development, and temperament.

PubMed

Fenstermacher, Susan K; Saudino, Kimberly J

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children's imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique.

Inclusion body myositis – pathomechanism and lessons from genetics

PubMed Central

Murnyák, Balázs; Bodoki, Levente; Vincze, Melinda; Griger, Zoltán; Csonka, Tamás; Szepesi, Rita; Kurucz, Andrea; Dankó, Katalin

2015-01-01

Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease. PMID:28352694

Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring.

PubMed

Hicks, Brian M; Foster, Katherine T; Iacono, William G; McGue, Matt

2013-10-01

Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. Participants were recruited from the community and assessed at a university laboratory. A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20). Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability than previously detected in twin studies and indicates that sibling rather than parent-child similarity indexes important environmental risk factors for externalizing disorders.

Dramatic genotypic difference in, and effect of genetic crossing on, tissue culture-induced mobility of retrotransposon Tos17 in rice.

PubMed

Lin, Chunjing; Lin, Xiuyun; Hu, Lanjuan; Yang, Jingjing; Zhou, Tianqi; Long, Likun; Xu, Chunming; Xing, Shaochen; Qi, Bao; Dong, Yingshan; Liu, Bao

2012-11-01

KEY MESSAGE : We show for the first time that intraspecific crossing may impact mobility of the prominent endogenous retrotransposon Tos17 under tissue culture conditions in rice. Tos17, an endogenous copia retrotransposon of rice, is transpositionally active in tissue culture. To study whether there exists fundamental genotypic difference in the tissue culture-induced mobility of Tos17, and if so, whether the difference is under genetic and/or epigenetic control, we conducted this investigation. We show that dramatic difference in tissue culture-induced Tos17 mobility exists among different rice pure-line cultivars sharing the same maternal parent: of the three lines studied that harbor Tos17, two showed mobilization of Tos17, which accrued in proportion to subculture duration, while the third line showed total quiescence (immobility) of the element and the fourth line did not contain the element. In reciprocal F1 hybrids between Tos17-mobile and -immobile (or absence) parental lines, immobility was dominant over mobility. In reciprocal F1 hybrids between both Tos17-mobile parental lines, an additive or synergistic effect on mobility of the element was noticed. In both types of reciprocal F1 hybrids, clear difference in the extent of Tos17 mobility was noted between crossing directions. Given that all lines share the same maternal parent, this observation indicates the existence of epigenetic parent-of-origin effect. We conclude that the tissue culture-induced mobility of Tos17 in rice is under complex genetic and epigenetic control, which can be either enhanced or repressed by intraspecific genetic crossing.

HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe.

PubMed

Inotai, D; Szilvasi, A; Benko, S; Boros-Major, A; Illes, Z; Bors, A; Kiss, K P; Rajczy, K; Gelle-Hossó, A; Buhler, S; Nunes, J M; Sanchez-Mazas, A; Tordai, A

2015-08-01

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic Advances in Autism: Heterogeneity and Convergence on Shared Pathways

PubMed Central

Bill, Brent R.; Geschwind, Daniel H.

2009-01-01

The autism spectrum disorders (ASD) are a heterogeneous set of developmental disorders characterized at their core by deficits in social interaction and communication. Current psychiatric nosology groups this broad set of disorders with strong genetic liability and multiple etiologies into the same diagnostic category. This heterogeneity has challenged genetic analyses. But shared patient resources, genomic technologies, more refined phenotypes, and novel computational approaches have begun to yield dividends in defining the genetic mechanisms at work. Over the last five years, a large number of autism susceptibility loci have emerged, redefining our notion of autism’s etiologies, and reframing how we think about ASD. PMID:19477629

Oppositional Defiant Disorder dimensions: genetic influences and risk for later psychopathology

PubMed Central

Mikolajewski, Amy J.; Taylor, Jeanette; Iacono, William G.

2016-01-01

Background This study was undertaken to determine how well two Oppositional Defiant Disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Methods Psychopathology was assessed via diagnostic interviews of 1225 twin pairs at ages 11 and 17. Results Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior, and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Conclusions Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. PMID:28059443

Oppositional defiant disorder dimensions: genetic influences and risk for later psychopathology.

PubMed

Mikolajewski, Amy J; Taylor, Jeanette; Iacono, William G

2017-06-01

This study was undertaken to determine how well two oppositional defiant disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Psychopathology was assessed via diagnostic interviews of 1,225 twin pairs at ages 11 and 17. Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed that the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. © 2017 Association for Child and Adolescent Mental Health.

Neural and Genetic Correlates of the Social Sharing of Happiness

PubMed Central

Matsunaga, Masahiro; Kawamichi, Hiroaki; Umemura, Tomohiro; Hori, Reiko; Shibata, Eiji; Kobayashi, Fumio; Suzuki, Kohta; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori; Ohira, Hideki

2017-01-01

Happiness is regarded as one of the most fundamental human goals. Given recent reports that positive feelings are contagious (e.g., the presence of a happy person enhances others' happiness) because of the human ability to empathize (i.e., sharing emotions), empathic ability may be a key factor in increasing one's own subjective level of happiness. Based on previous studies indicating that a single nucleotide polymorphism in the serotonin 2A receptor gene [HTR2A rs6311 guanine (G) vs. adenine (A)] is associated with sensitivity to emotional stimuli and several mental disorders such as depression, we predicted that the polymorphism might be associated with the effect of sharing happiness. To elucidate the neural and genetic correlates of the effect of sharing happiness, we first performed functional magnetic resonance imaging (fMRI) during a “happy feelings” evocation task (emotional event imagination task), during which we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend experiencing a positive-valence event (presence or absence). We recruited young adult women for this fMRI study because empathic ability may be higher in women than in men. Participants felt happier (p < 0.01) and the mentalizing/theory-of-mind network, which spans the medial prefrontal cortex, temporoparietal junction, temporal poles, and precuneus, was significantly more active (p < 0.05) in the presence condition than in the absence condition regardless of event valence. Moreover, participants with the GG (p < 0.01) and AG (p < 0.05) genotypes of HTR2A experienced happier feelings as well as greater activation of a part of the mentalizing/theory-of-mind network (p < 0.05) during empathy for happiness (neutral/presence condition) than those with the AA genotype. In a follow-up study with a vignette-based questionnaire conducted in a relatively large sample, male and female participants were presented with the same imagined events wherein their valence and the presence of a friend were manipulated. Results showed genetic differences in happiness-related empathy regardless of sex (p < 0.05). Findings suggest that HTR2A polymorphisms are associated with the effect of sharing happiness by modulating the activity of the mentalizing/theory-of-mind network. PMID:29311795

Neural and Genetic Correlates of the Social Sharing of Happiness.

PubMed

Matsunaga, Masahiro; Kawamichi, Hiroaki; Umemura, Tomohiro; Hori, Reiko; Shibata, Eiji; Kobayashi, Fumio; Suzuki, Kohta; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori; Ohira, Hideki

2017-01-01

Happiness is regarded as one of the most fundamental human goals. Given recent reports that positive feelings are contagious (e.g., the presence of a happy person enhances others' happiness) because of the human ability to empathize (i.e., sharing emotions), empathic ability may be a key factor in increasing one's own subjective level of happiness. Based on previous studies indicating that a single nucleotide polymorphism in the serotonin 2A receptor gene [ HTR2A rs6311 guanine (G) vs. adenine (A)] is associated with sensitivity to emotional stimuli and several mental disorders such as depression, we predicted that the polymorphism might be associated with the effect of sharing happiness. To elucidate the neural and genetic correlates of the effect of sharing happiness, we first performed functional magnetic resonance imaging (fMRI) during a "happy feelings" evocation task (emotional event imagination task), during which we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend experiencing a positive-valence event (presence or absence). We recruited young adult women for this fMRI study because empathic ability may be higher in women than in men. Participants felt happier ( p < 0.01) and the mentalizing/theory-of-mind network, which spans the medial prefrontal cortex, temporoparietal junction, temporal poles, and precuneus, was significantly more active ( p < 0.05) in the presence condition than in the absence condition regardless of event valence. Moreover, participants with the GG ( p < 0.01) and AG ( p < 0.05) genotypes of HTR2A experienced happier feelings as well as greater activation of a part of the mentalizing/theory-of-mind network ( p < 0.05) during empathy for happiness (neutral/presence condition) than those with the AA genotype. In a follow-up study with a vignette-based questionnaire conducted in a relatively large sample, male and female participants were presented with the same imagined events wherein their valence and the presence of a friend were manipulated. Results showed genetic differences in happiness-related empathy regardless of sex ( p < 0.05). Findings suggest that HTR2A polymorphisms are associated with the effect of sharing happiness by modulating the activity of the mentalizing/theory-of-mind network.

Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

PubMed

Gu, Yulong; Warren, James Roy; Day, Karen Jean

2011-01-01

This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR.

PubMed

Momeni, Stephanie S; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A; Childers, Noel K

2016-09-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1-9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 157 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR

PubMed Central

Momeni, Stephanie S.; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A.; Childers, Noel K.

2016-01-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1–9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 155 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. PMID:27432341

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

Why do identical twins differ in personality: shared environment reconsidered.

PubMed

Torgersen, Anne Mari; Janson, Harald

2002-02-01

While heritability studies show that most of the variance in adult personality can be attributed to genetic or so-called nonshared environmental influence, this does not mean that shared events lack importance for the development of later personality differences. We studied the relationship between Big Five personality differences in monozygotic (MZ) twins at age 29, and life stressors at age 6 to 15, using prospective data from 26 MZ pairs studied from birth onwards. A positive significant correlation was found between stressors in childhood and early adolescence, and intrapair personality differences in Agreeableness, Openness, Conscientiousness, and five-factor profiles. We note that the effects of shared events are labeled "nonshared" environment when the effect is to make siblings more different. Case examples illustrate the relationship between stress and personality differences, and provide hypotheses for further studies in larger samples.

Genetic specificity of face recognition.

PubMed

Shakeshaft, Nicholas G; Plomin, Robert

2015-10-13

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

Genetic specificity of face recognition

PubMed Central

Shakeshaft, Nicholas G.; Plomin, Robert

2015-01-01

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities. PMID:26417086

Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

ERIC Educational Resources Information Center

Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

2010-01-01

People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

Literacy outcomes of children with early childhood speech sound disorders: impact of endophenotypes.

PubMed

Lewis, Barbara A; Avrich, Allison A; Freebairn, Lisa A; Hansen, Amy J; Sucheston, Lara E; Kuo, Iris; Taylor, H Gerry; Iyengar, Sudha K; Stein, Catherine M

2011-12-01

To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills.

Literacy Outcomes of Children With Early Childhood Speech Sound Disorders: Impact of Endophenotypes

PubMed Central

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2012-01-01

Purpose To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method Children with SSD and their siblings were assessed at early childhood (ages 4–6 years) and followed at school age (7–12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Results Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Conclusions Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills. PMID:21930616

Genetics of Attention Deficit Hyperactivity Disorder: A Current Review and Future Prospects

ERIC Educational Resources Information Center

Levy, Florence; Hay, David A.; Bennett, Kellie S.

2006-01-01

While there have been significant advances in both the behaviour genetics and molecular genetics of Attention Deficit Hyperactivity Disorder (ADHD), researchers are now beginning to develop hypotheses about relationships between phenotypes and genetic mechanisms. Twin studies are able to model genetic, shared environmental and non-shared…

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

PubMed Central

He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

2016-01-01

Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

Meta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Loci

PubMed Central

Zhernakova, Alexandra; Stahl, Eli A.; Trynka, Gosia; Raychaudhuri, Soumya; Festen, Eleanora A.; Franke, Lude; Westra, Harm-Jan; Fehrmann, Rudolf S. N.; Kurreeman, Fina A. S.; Thomson, Brian; Gupta, Namrata; Romanos, Jihane; McManus, Ross; Ryan, Anthony W.; Turner, Graham; Brouwer, Elisabeth; Posthumus, Marcel D.; Remmers, Elaine F.; Tucci, Francesca; Toes, Rene; Grandone, Elvira; Mazzilli, Maria Cristina; Rybak, Anna; Cukrowska, Bozena; Coenen, Marieke J. H.; Radstake, Timothy R. D. J.; van Riel, Piet L. C. M.; Li, Yonghong; de Bakker, Paul I. W.; Gregersen, Peter K.; Worthington, Jane; Siminovitch, Katherine A.; Klareskog, Lars; Huizinga, Tom W. J.

2011-01-01

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5×10−8 in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (Pcombined = 1.2×10−12), rs864537 near CD247 (Pcombined = 2.2×10−11), rs2298428 near UBE2L3 (Pcombined = 2.5×10−10), and rs11203203 near UBASH3A (Pcombined = 1.1×10−8). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5×10−8 (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases. PMID:21383967

Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

PubMed

Zhernakova, Alexandra; Stahl, Eli A; Trynka, Gosia; Raychaudhuri, Soumya; Festen, Eleanora A; Franke, Lude; Westra, Harm-Jan; Fehrmann, Rudolf S N; Kurreeman, Fina A S; Thomson, Brian; Gupta, Namrata; Romanos, Jihane; McManus, Ross; Ryan, Anthony W; Turner, Graham; Brouwer, Elisabeth; Posthumus, Marcel D; Remmers, Elaine F; Tucci, Francesca; Toes, Rene; Grandone, Elvira; Mazzilli, Maria Cristina; Rybak, Anna; Cukrowska, Bozena; Coenen, Marieke J H; Radstake, Timothy R D J; van Riel, Piet L C M; Li, Yonghong; de Bakker, Paul I W; Gregersen, Peter K; Worthington, Jane; Siminovitch, Katherine A; Klareskog, Lars; Huizinga, Tom W J; Wijmenga, Cisca; Plenge, Robert M

2011-02-01

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined) =  1.2 × 10(-12)), rs864537 near CD247 (P(combined) =  2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined) =  2.5 × 10(-10)), and rs11203203 near UBASH3A (P(combined) =  1.1 × 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

PubMed

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

Musculoskeletal complaints, anxiety-depression symptoms, and neuroticism: A study of middle-aged twins.

PubMed

Vassend, Olav; Røysamb, Espen; Nielsen, Christopher Sivert; Czajkowski, Nikolai Olavi

2017-08-01

Musculoskeletal (MS) complaints are reported commonly, but the extent to which such complaints reflect the severity of site-specific pathology or a more generalized susceptibility to feel pain/discomfort is uncertain. Both site-specific and more widespread MS conditions have been shown to be linked to anxiety and depression, but the nature of this relationship is poorly understood. In the present study the role of neuroticism as a shared risk factor that may possibly explain the co-occurrence between anxiety-depression and MS complaints was investigated. The sample consisted of 746 monozygotic and 770 dizygotic twins in the age group of 50-65 years (M = 57.11, SD = 4.5). Using Cholesky modeling, genetic and environmental influences on neuroticism, anxiety-depression and MS symptoms, and the associations among these phenotypes were determined. A single factor accounted for about 50% of the overall variance in MS symptom reporting. The best-fitting biometric model included sex-specific additive genetic and individual-specific environmental effects. All 3 phenotypes were strongly influenced by genetic factors, heritability (h2) = 0.41-0.56. Furthermore, while there was a considerable overlap in genetic risk factors among the 3 phenotypes, a substantial proportion of the genetic risk shared between MS complaints and anxiety-depression was independent of neuroticism. Evidence for a common underlying susceptibility to report MS symptoms, genetically linked to both neuroticism and anxiety-depression symptoms, was found. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Alcoholic Marriage: Later Start, Sooner End

PubMed Central

Waldron, Mary; Heath, Andrew C.; Lynskey, Michael T.; Bucholz, Kathleen K.; Madden, Pamela A. F.; Martin, Nicholas G.

2010-01-01

Background Although associations between drinking behavior and marital status are well documented, timing of marital transitions as a function of alcohol use or disorder has received limited empirical attention. Methods We examine the relationship between lifetime history of alcohol dependence (AD) and timing and survival of first marriages in a sample of 3575 female and 1845 male adult Australian twins born mostly between 1940 and 1964. Survival analyses were conducted using Cox proportional hazards regression models. Results Results indicate moderate delays in marriage associated with AD for both women and men. Among ever married respondents, AD was strongly predictive of early separation, with similar effects observed for women and men. Heritable sources of covariation were also documented. For women, genetic influences shared between early-onset AD and marital timing were found. Genetic influences shared between AD and marital survival were observed for women without regard to onset and for men with later-onset AD. Conclusions Results confirm the importance of AD as a predictor of both timing and survival of first marriages, with genetic influences contributing to observed associations. PMID:21244438

Exploring how nature and nurture affect the development of reading: An analysis of the Florida Twin Project on Reading

PubMed Central

Hart, Sara A.; Logan, Jessica A.R.; Soden-Hensler, Brooke; Kershaw, Sarah; Taylor, Jeanette; Schatschneider, Christopher

2013-01-01

Research on the development of reading skills through the primary school years has pointed to the importance of individual differences in initial ability as well as the growth of those skills. Additionally, it has been theorized that reading skills develop incrementally. The present study examined the genetic and environmental influences on two developmental models representing these parallel ideas, generalizing the findings to explore the processes of reading development. Participants were drawn from the Florida Twin Project on Reading, with a total of 2370 pairs of twins’ representative of the state of Florida. Twins’ oral reading fluency scores from school progress monitoring records collected in the fall of grades 1 through 5 were used to model development. Results suggested that genetic influences on the development of reading are general, shared across the early school years, as well as novel, with new genetic influences introduced at each of the first three years of school. The shared environment estimates suggest a pattern of general influences only, suggesting environmental effects which are moderate and stable across development. PMID:23294149

The companion dog as a unique translational model for aging.

PubMed

Mazzatenta, Andrea; Carluccio, Augusto; Robbe, Domenico; Giulio, Camillo Di; Cellerino, Alessandro

2017-10-01

The dog is a unique species due to its wide variation among breeds in terms of size, morphology, behaviour and lifespan, coupled with a genetic structure that facilitates the dissection of the genetic architecture that controls these traits. Dogs and humans co-evolved and share recent evolutionary selection processes, such as adaptation to digest starch-rich diets. Many diseases of the dog have a human counterpart, and notably Alzheimer's disease, which is otherwise difficult to model in other organisms. Unlike laboratory animals, companion dogs share the human environment and lifestyle, are exposed to the same pollutants, and are faced with pathogens and infections. Dogs represented a very useful model to understand the relationship between size, insulin-like growth factor-1 genetic variation and lifespan, and have been used to test the effects of dietary restriction and immunotherapy for Alzheimer's disease. Very recently, rapamycin was tested in companion dogs outside the laboratory, and this approach where citizens are involved in research aimed at the benefit of dog welfare might become a game changer in geroscience. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does education confer a culture of healthy behavior? Smoking and drinking patterns in Danish twins.

PubMed

Johnson, Wendy; Kyvik, Kirsten Ohm; Mortensen, Erik L; Skytthe, Axel; Batty, G David; Deary, Ian J

2011-01-01

More education is associated with healthier smoking and drinking behaviors. Most analyses of effects of education focus on mean levels. Few studies have compared variance in health-related behaviors at different levels of education or analyzed how education impacts underlying genetic and environmental sources of health-related behaviors. This study explored these influences. In a 2002 postal questionnaire, 21,522 members of the Danish Twin Registry, born during 1931-1982, reported smoking and drinking habits. The authors used quantitative genetic models to examine how these behaviors' genetic and environmental variances differed with level of education, adjusting for birth-year effects. As expected, more education was associated with less smoking, and average drinking levels were highest among the most educated. At 2 standard deviations above the mean educational level, variance in smoking and drinking was about one-third that among those at 2 standard deviations below, because fewer highly educated people reported high levels of smoking or drinking. Because shared environmental variance was particularly restricted, one explanation is that education created a culture that discouraged smoking and heavy drinking. Correlations between shared environmental influences on education and the health behaviors were substantial among the well-educated for smoking in both sexes and drinking in males, reinforcing this notion.

The impact of sleep duration on adolescent development: a genetically informed analysis of identical twin pairs.

PubMed

Barnes, J C; Meldrum, Ryan C

2015-02-01

Recent work provides evidence that reduced sleep duration has detrimental effects on a range of developmentally related outcomes during adolescence. Yet, the potential confounding influence of genetic and shared environmental effects has not been sufficiently addressed. This study addresses this issue by analyzing cross-sectional data from the twin sub-sample of the first wave of the National Longitudinal Study of Adolescent Health [N ≈ 287 MZ (monozygotic) twin pairs; 50% male; 22% Black; mean age = 15.75]. Associations between sleep duration (measured through two different strategies, one tapping number of hours slept at night and the other measuring weeknight bedtimes) and seven outcomes (self-control, depressive symptoms, suicidal ideation, body mass index, violent delinquency, non-violent delinquency, and drug use) were estimated. Consistent with prior research, associations between sleep duration and several outcomes were statistically significant when using standard social science analytic methods. Yet, when employing a methodology that accounts for genetic and shared environmental influences, some of these associations were reduced to non-significance. Still, two consistent associations remained in that participants who reported sleeping fewer hours at night (or who reported later bedtimes) exhibited lower levels of self-control and more depressive symptoms. Implications of the findings and directions for future research are discussed.

Identification of salt-tolerant QTLs with strong genetic background effect using two sets of reciprocal introgression lines in rice.

PubMed

Cheng, Lirui; Wang, Yun; Meng, Lijun; Hu, Xia; Cui, Yanru; Sun, Yong; Zhu, Linghua; Ali, Jauhar; Xu, Jianlong; Li, Zhikang

2012-01-01

Effect of genetic background on detection of quantitative trait locus (QTL) governing salinity tolerance (ST) was studied using two sets of reciprocal introgression lines (ILs) derived from a cross between a moderately salinity tolerant japonica variety, Xiushui09 from China, and a drought tolerant but salinity susceptible indica breeding line, IR2061-520-6-9 from the Philippines. Salt toxicity symptoms (SST) on leaves, days to seedling survival (DSS), and sodium and potassium uptake by shoots were measured under salinity stress of 140 mmol/L of NaCl. A total of 47 QTLs, including 26 main-effect QTLs (M-QTLs) and 21 epistatic QTLs (E-QTLs), were identified from the two sets of reciprocal ILs. Among the 26 M-QTLs, only four (15.4%) were shared in the reciprocal backgrounds while no shared E-QTLs were detected, indicating that ST QTLs, especially E-QTLs, were very specific to the genetic background. Further, 78.6% of the M-QTLs for SST and DSS identified in the reciprocal ILs were also detected in the recombinant inbred lines (RILs) from the same cross, which clearly brings out the background effect on ST QTL detection and its utilization in ST breeding. The detection of ILs with various levels of pyramiding of nonallelic M-QTL alleles for ST from Xiushui09 into IR2061-520-6-9 allowed us to further improve the ST in rice.

The genomic landscape of rapid, repeated evolutionary rescue from toxic pollution in wild fish

USDA-ARS?s Scientific Manuscript database

Several populations of Atlantic killifish (Fundulus heteroclitus) in contaminated Atlantic coast estuaries have evolved resistance to the toxic effects of PCBs, dioxins, and PAHs. However, the genetic mechanisms of resistance and whether they are shared among populations is not known. We sequenced t...

Sexual offending runs in families: A 37-year nationwide study

PubMed Central

Långström, Niklas; Babchishin, Kelly M; Fazel, Seena; Lichtenstein, Paul; Frisell, Thomas

2015-01-01

Background: Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. Methods: We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21 566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. Results: We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5–5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2–4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5–2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2–2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). Conclusions: We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment. PMID:25855722

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.

Resilience and risk for alcohol use disorders: A Swedish twin study

PubMed Central

Long, E.C.; Lönn, S.L.; Ji, J.; Lichtenstein, P.; Sundquist, J.; Sundquist, K.; Kendler, K.S.

2016-01-01

Background Resilience has been shown to be protective against alcohol use disorders (AUD), but the magnitude and nature of the relationship between these two phenotypes is not clear. The aim of this study is to examine the strength of this relationship and the degree to which it results from common genetic or common environmental influences. Methods Resilience was assessed on a nine-point scale during a personal interview in 1,653,721 Swedish men aged 17–25 years. AUD was identified based on Swedish medical, legal, and pharmacy registries. The magnitude of the relationship between resilience and AUD was examined using logistic regression. The extent to which the relationship arises from common genetic or common environmental factors was examined using a bivariate Cholesky decomposition model. Results The five single items that comprised the resilience assessment (social maturity, interest, psychological energy, home environment, and emotional control) all reduced risk for subsequent AUD, with social maturity showing the strongest effect. The linear effect by logistic regression showed that a one-point increase on the resilience scale was associated with a 29% decrease in odds of AUD. The Cholesky decomposition model demonstrated that the resilience-AUD relationship was largely attributable to overlapping genetic and shared environmental factors (57% and 36%, respectively). Conclusion Resilience is strongly associated with a reduction in risk for AUD. This relationship appears to be the result of overlapping genetic and shared environmental influences that impact resilience and risk of AUD, rather than a directly causal relationship. PMID:27918840

Admixture into and within sub-Saharan Africa

PubMed Central

Busby, George BJ; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris CA

2016-01-01

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001 PMID:27324836

Extensive shared polymorphism at non-MHC immune genes in recently diverged North American prairie grouse

USGS Publications Warehouse

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2018-01-01

Gene polymorphisms shared between recently diverged species are thought to be widespread and most commonly reflect introgression from hybridization or retention of ancestral polymorphism through incomplete lineage sorting. Shared genetic diversity resulting from incomplete lineage sorting is usually maintained for a relatively short period of time, but under strong balancing selection it may persist for millions of years beyond species divergence (balanced trans-species polymorphism), as in the case of the major histocompatibility complex (MHC) genes. However, balancing selection is much less likely to act on non-MHC immune genes. The aim of this study was to investigate the patterns of shared polymorphism and selection at non-MHC immune genes in five grouse species from Centrocercus and Tympanuchus genera. For this purpose, we genotyped five non-MHC immune genes that do not interact directly with pathogens, but are involved in signaling and regulate immune cell growth. In contrast to previous studies with MHC, we found no evidence for balancing selection or balanced trans-species polymorphism among the non-MHC immune genes. No haplotypes were shared between genera and in most cases more similar allelic variants sorted by genus. Between species within genera, however, we found extensive shared polymorphism, which was most likely attributable to introgression or incomplete lineage sorting following recent divergence and large ancestral effective population size (i.e., weak genetic drift). Our study suggests that North American prairie grouse may have attained relatively low degree of reciprocal monophyly at nuclear loci and reinforces the rarity of balancing selection in non-MHC immune genes.

Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry.

PubMed

Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

2010-06-11

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads.

Abraham's Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry

PubMed Central

Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

2010-01-01

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads. PMID:20560205

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

PubMed

Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

2017-10-01

Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings.

PubMed

Agrawal, Arpana; Grant, Julia D; Lynskey, Michael T; Madden, Pamela A F; Heath, Andrew C; Bucholz, Kathleen K; Sartor, Carolyn E

2016-06-01

Use of cigarettes and cannabis frequently co-occurs. We examine the role of genetic and environmental influences on variation in and covariation between tobacco cigarette and cannabis use across European-American (EA) and African-American (AA) women. Data on lifetime cannabis and cigarette use were drawn from interviews of 956 AA and 3557 EA young adult female twins and non-twin same sex female full siblings. Twin modeling was used to decompose variance in and covariance between cigarette and cannabis use into additive genetic, shared, special twin and non-shared environmental sources. Cigarette use was more common in EAs (75.3%, 95% C.I. 73.8-76.7%) than AAs (64.2%, 95% C.I. 61.2-67.2%) while cannabis use was marginally more commonly reported by AAs (55.5%, 95% C.I. 52.5-58.8%) than EAs (52.4%, 95% C.I. 50.7-54.0%). Additive genetic factors were responsible for 43-66% of the variance in cigarette and cannabis use. Broad shared environmental factors (shared+special twin) played a more significant role in EA (23-29%) than AA (2-15%) women. In AA women, the influence of non-shared environment was more pronounced (42-45% vs. 11-19% in EA women). There was strong evidence for the same familial influences underlying use of both substances (rA=0.82-0.89; rC+T=0.70-0.75). Non-shared environmental factors were also correlated but less so (rE=0.48-0.66). No racial/ethnic differences were apparent in these sources of covariation. Heritability of cigarette and cannabis use is comparable across racial/ethnic groups. Differences in the contribution of shared and non-shared environmental influences indicate that different factors may shape substance use in EA and AA women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rearing Environmental Influences on Religiousness: An Investigation of Adolescent Adoptees.

PubMed

Koenig, Laura B; McGue, Matt; Iacono, William G

2009-10-01

Religiousness is widely considered to be a culturally transmitted trait. However, twin studies suggest that religiousness is genetically influenced in adulthood, although largely environmentally influenced in childhood/adolescence. We examined genetic and environmental influences on a self-report measure of religiousness in a sample consisting of 284 adoptive families (two adopted adolescent siblings and their rearing parents); 208 biological families (two full biological adolescent siblings and their parents); and 124 mixed families (one adopted and one biological adolescent sibling and their parents). A sibling-family model was fit to the data to estimate genetic, shared environmental, and nonshared environmental effects on religiousness, as well as cultural transmission and assortative mating effects. Religiousness showed little evidence of heritability and large environmental effects, which did not vary significantly by gender. This finding is consistent with the results of twin studies of religiousness in adolescent and preadolescent samples.

Rearing Environmental Influences on Religiousness: An Investigation of Adolescent Adoptees

PubMed Central

Koenig, Laura B.; McGue, Matt; Iacono, William G.

2009-01-01

Religiousness is widely considered to be a culturally transmitted trait. However, twin studies suggest that religiousness is genetically influenced in adulthood, although largely environmentally influenced in childhood/adolescence. We examined genetic and environmental influences on a self-report measure of religiousness in a sample consisting of 284 adoptive families (two adopted adolescent siblings and their rearing parents); 208 biological families (two full biological adolescent siblings and their parents); and 124 mixed families (one adopted and one biological adolescent sibling and their parents). A sibling-family model was fit to the data to estimate genetic, shared environmental, and nonshared environmental effects on religiousness, as well as cultural transmission and assortative mating effects. Religiousness showed little evidence of heritability and large environmental effects, which did not vary significantly by gender. This finding is consistent with the results of twin studies of religiousness in adolescent and preadolescent samples. PMID:20161346

78 FR 13286 - Sharing Certain Business Information Regarding the Introduction of Genetically Engineered...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... Information Regarding the Introduction of Genetically Engineered Organisms With State and Tribal Government... proposing to amend our regulations regarding genetically engineered organisms regulated by the United States...). The regulations refer to such genetically engineered (GE) organisms and products as ``regulated...

Bartonellae are Prevalent and Diverse in Costa Rican Bats and Bat Flies.

PubMed

Judson, S D; Frank, H K; Hadly, E A

2015-12-01

Species in the bacterial genus, Bartonella, can cause disease in both humans and animals. Previous reports of Bartonella in bats and ectoparasitic bat flies suggest that bats could serve as mammalian hosts and bat flies as arthropod vectors. We compared the prevalence and genetic similarity of bartonellae in individual Costa Rican bats and their bat flies using molecular and sequencing methods targeting the citrate synthase gene (gltA). Bartonellae were more prevalent in bat flies than in bats, and genetic variants were sometimes, but not always, shared between bats and their bat flies. The detected bartonellae genetic variants were diverse, and some were similar to species known to cause disease in humans and other mammals. The high prevalence and sharing of bartonellae in bat flies and bats support a role for bat flies as a potential vector for Bartonella, while the genetic diversity and similarity to known species suggest that bartonellae could spill over into humans and animals sharing the landscape. © 2015 Blackwell Verlag GmbH.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations.

PubMed

Kopelman, Naama M; Stone, Lewi; Wang, Chaolong; Gefel, Dov; Feldman, Marcus W; Hillel, Jossi; Rosenberg, Noah A

2009-12-08

Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

PubMed Central

2009-01-01

Background Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. Results We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. Conclusion These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent. PMID:19995433

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

PubMed Central

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

Cis-regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans

PubMed Central

Miller, Craig T.; Beleza, Sandra; Pollen, Alex A.; Schluter, Dolph; Kittles, Rick A.; Shriver, Mark D.; Kingsley, David M.

2010-01-01

SUMMARY Dramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg) gene. The divergent allele reduces expression in gill and skin tissue, and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans. PMID:18083106

Individual Differences in Exercise Behavior: Stability and Change in Genetic and Environmental Determinants From Age 7 to 18.

PubMed

Huppertz, Charlotte; Bartels, Meike; de Zeeuw, Eveline L; van Beijsterveldt, Catharina E M; Hudziak, James J; Willemsen, Gonneke; Boomsma, Dorret I; de Geus, Eco J C

2016-09-01

Exercise behavior during leisure time is a major source of health-promoting physical activity and moderately tracks across childhood and adolescence. This study aims to investigate the absolute and relative contribution of genes and the environment to variance in exercise behavior from age 7 to 18, and to elucidate the stability and change of genetic and shared environmental factors that underlie this behavior. The Netherlands Twin Register collected data on exercise behavior in twins aged approximately 7, 10, 12, 14, 16 and 18 years (N = 27,332 twins; 48 % males; 47 % with longitudinal assessments). Three exercise categories (low, middle, high) were analyzed by means of liability threshold models. First, a univariate model was fitted using the largest available cross-sectional dataset with linear and quadratic effects of age as modifiers on the means and variance components. Second, a simplex model was fitted on the longitudinal dataset. Heritability was low in 7-year-olds (14 % in males and 12 % in females), but gradually increased up to age 18 (79 % in males and 49 % in females), whereas the initially substantial relative influence of the shared environment decreased with age (from 80 to 4 % in males and from 80 to 19 % in females). This decrease was due to a large increase in the genetic variance. The longitudinal model showed the genetic effects in males to be largely stable and to accumulate from childhood to late adolescence, whereas in females, they were marked by both transmission and innovation at all ages. The shared environmental effects tended to be less stable in both males and females. In sum, the clear age-moderation of exercise behavior implies that family-based interventions might be useful to increase this behavior in children, whereas individual-based interventions might be better suited for adolescents. We showed that some determinants of individual differences in exercise behavior are stable across childhood and youth, whereas others come into play at specific ages. In view of the many benefits of regular exercise, identifying these determinants at specific ages should be a public health priority.

Shared-environmental contributions to high cognitive ability.

PubMed

Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

2009-07-01

Using a combined sample of adolescent twins, biological siblings, and adoptive siblings, we estimated and compared the differential shared-environmentality for high cognitive ability and the shared-environmental variance for the full range of ability during adolescence. Estimates obtained via multiple methods were in the neighborhood of 0.20, and suggest a modest effect of the shared environment on both high and full-range ability. We then examined the association of ability with three measures of the family environment in a subsample of adoptive siblings: parental occupational status, parental education, and disruptive life events. Only parental education showed significant (albeit modest) association with ability in both the biological and adoptive samples. We discuss these results in terms of the need for cognitive-development research to combine genetically sensitive designs and modern statistical methods with broad, thorough environmental measurement.

Medical Genetics and the First Studies of the Genetics of Populations in Mexico.

PubMed

Barahona, Ana

2016-09-01

Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. Copyright © 2016 by the Genetics Society of America.

Redefining genomic privacy: trust and empowerment.

PubMed

Erlich, Yaniv; Williams, James B; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D; Witkowski, Jan A; Kain, Robert C

2014-11-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.

Redefining Genomic Privacy: Trust and Empowerment

PubMed Central

Erlich, Yaniv; Williams, James B.; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D.; Witkowski, Jan A.; Kain, Robert C.

2014-01-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research. PMID:25369215

The U.S. Culture Collection Network Responding to the Requirements of the Nagoya Protocol on Access and Benefit Sharing

PubMed Central

Barker, Katharine B.; Barton, Hazel A.; Boundy-Mills, Kyria; Brown, Daniel R.; Coddington, Jonathan A.; Cook, Kevin; Desmeth, Philippe; Geiser, David; Glaeser, Jessie A.; Greene, Stephanie; Kang, Seogchan; Lomas, Michael W.; Melcher, Ulrich; Miller, Scott E.; Nobles, David R.; Owens, Kristina J.; Reichman, Jerome H.; da Silva, Manuela; Wertz, John; Whitworth, Cale; Smith, David

2017-01-01

ABSTRACT The U.S. Culture Collection Network held a meeting to share information about how culture collections are responding to the requirements of the recently enacted Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity (CBD). The meeting included representatives of many culture collections and other biological collections, the U.S. Department of State, U.S. Department of Agriculture, Secretariat of the CBD, interested scientific societies, and collection groups, including Scientific Collections International and the Global Genome Biodiversity Network. The participants learned about the policies of the United States and other countries regarding access to genetic resources, the definition of genetic resources, and the status of historical materials and genetic sequence information. Key topics included what constitutes access and how the CBD Access and Benefit-Sharing Clearing-House can help guide researchers through the process of obtaining Prior Informed Consent on Mutually Agreed Terms. U.S. scientists and their international collaborators are required to follow the regulations of other countries when working with microbes originally isolated outside the United States, and the local regulations required by the Nagoya Protocol vary by the country of origin of the genetic resource. Managers of diverse living collections in the United States described their holdings and their efforts to provide access to genetic resources. This meeting laid the foundation for cooperation in establishing a set of standard operating procedures for U.S. and international culture collections in response to the Nagoya Protocol. PMID:28811341

The U.S. Culture Collection Network Responding to the Requirements of the Nagoya Protocol on Access and Benefit Sharing.

PubMed

McCluskey, Kevin; Barker, Katharine B; Barton, Hazel A; Boundy-Mills, Kyria; Brown, Daniel R; Coddington, Jonathan A; Cook, Kevin; Desmeth, Philippe; Geiser, David; Glaeser, Jessie A; Greene, Stephanie; Kang, Seogchan; Lomas, Michael W; Melcher, Ulrich; Miller, Scott E; Nobles, David R; Owens, Kristina J; Reichman, Jerome H; da Silva, Manuela; Wertz, John; Whitworth, Cale; Smith, David

2017-08-15

The U.S. Culture Collection Network held a meeting to share information about how culture collections are responding to the requirements of the recently enacted Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity (CBD). The meeting included representatives of many culture collections and other biological collections, the U.S. Department of State, U.S. Department of Agriculture, Secretariat of the CBD, interested scientific societies, and collection groups, including Scientific Collections International and the Global Genome Biodiversity Network. The participants learned about the policies of the United States and other countries regarding access to genetic resources, the definition of genetic resources, and the status of historical materials and genetic sequence information. Key topics included what constitutes access and how the CBD Access and Benefit-Sharing Clearing-House can help guide researchers through the process of obtaining Prior Informed Consent on Mutually Agreed Terms. U.S. scientists and their international collaborators are required to follow the regulations of other countries when working with microbes originally isolated outside the United States, and the local regulations required by the Nagoya Protocol vary by the country of origin of the genetic resource. Managers of diverse living collections in the United States described their holdings and their efforts to provide access to genetic resources. This meeting laid the foundation for cooperation in establishing a set of standard operating procedures for U.S. and international culture collections in response to the Nagoya Protocol.

Overlap and specificity of genetic and environmental influences on mathematics and reading disability in 10-year-old twins

PubMed Central

Kovas, Y.; Haworth, C.M.A.; Harlaar, N.; Petrill, S.A.; Dale, P.S.; Plomin, R.

2009-01-01

Background To what extent do genetic and environmental influences on reading disability overlap with those on mathematics disability? Multivariate genetic research on the normal range of variation in unselected samples has led to a Generalist Genes Hypothesis which posits that the same genes largely affect individual differences in these abilities in the normal range. However, little is known about the etiology of co-morbidity for the disability extremes of reading and mathematics. Method From 2596 pairs of 10-year-old monozygotic and dizygotic twins assessed on a web-based battery of reading and mathematics tests, we selected the lowest 15% on reading and on mathematics. We conducted bivariate DeFries–Fulker (DF) extremes analyses to assess overlap and specificity of genetic and environmental influences on reading and mathematics disability defined by a 15% cut-off. Results Both reading and mathematics disability are moderately heritable (47% and 43%, respectively) and show only modest shared environmental influence (16% and 20%). There is substantial phenotypic co-morbidity between reading and mathematics disability. Bivariate DF extremes analyses yielded a genetic correlation of .67 between reading disability and mathematics disability, suggesting that they are affected largely by the same genetic factors. The shared environmental correlation is .96 and the non-shared environmental correlation is .08. Conclusions In line with the Generalist Genes Hypothesis, the same set of generalist genes largely affects mathematical and reading disabilities. The dissociation between the disabilities occurs largely due to independent non-shared environmental influences. PMID:17714376

Approaching confidentiality at a familial level in genomic medicine: a focus group study with healthcare professionals

PubMed Central

Dheensa, Sandi; Fenwick, Angela; Lucassen, Anneke

2017-01-01

Objectives Clinical genetics guidelines from 2011 conceptualise genetic information as confidential to families, not individuals. The normative consequence of this is that the family's interest is the primary consideration and genetic information is shared unless there are good reasons not to do so. We investigated healthcare professionals' (HCPs') views about, and reasoning around, individual and familial approaches to confidentiality and how such views influenced their practice. Method 16 focus groups with 80 HCPs working in/with clinical genetics services were analysed, drawing on grounded theory. Results Participants raised seven problems with, and arguments against, going beyond the individual approach to confidentiality. These problems fell into two overlapping categories: ‘relationships’ and ‘structures’. Most participants had never considered ways to—or thought it was impossible to—treat familial genetic information and personal information differently. They worried that putting the familial approach into practice could disrupt family dynamics and erode patient trust in the health service. They also thought they had insufficient resources to share information and feared that sharing might change the standard of care and make them more vulnerable to liability. Conclusions A familial approach to confidentiality has not been accepted or adopted as a standard, but wider research suggests that some of the problems HCPs perceived are surmountable and sharing in the interest of the family can be achieved. However, further research is needed to explore how personal and familial genetic information can be separated in practice. Our findings are relevant to HCPs across health services who are starting to use genome tests as part of their routine investigations. PMID:28159847

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

PubMed Central

Robinson, Elise B.; Kirby, Andrew; Ruparel, Kosha; Yang, Jian; McGrath, Lauren; Anttila, Verneri; Neale, Benjamin M.; Merikangas, Kathleen; Lehner, Thomas; Sleiman, Patrick M.A.; Daly, Mark J.; Gur, Ruben; Gur, Raquel; Hakonarson, Hakon

2014-01-01

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. PMID:25023143

Genetics objective structured clinical exams at the Maimonides Infants & Children's Hospital of Brooklyn, New York.

PubMed

Altshuler, Lisa; Kachur, Elizabeth; Krinshpun, Shifra; Sullivan, Deborah

2008-11-01

In 2003, the Maimonides Infants & Children's Hospital received a Title VII Residency Training in Primary Care grant to integrate genetic-specific competencies into postgraduate pediatrics education. As part of that endeavor, mandatory yearly genetics objective structured clinical exams (OSCEs) were instituted for third-year residents. This article reports on the first three years of experience with this innovative educational tool.After an overview of genetic concepts, dysmorphology, and communication styles, residents complete a five-station OSCE and receive feedback from standardized patients and from the faculty who observe them. After this clinical exercise, the residents participate in a small-group debriefing session to share strategies for effective communication and clinical case management and to discuss the ethical issues that arise with these genetic cases.In three years, 60 residents have completed the genetics OSCE program. Evaluation data demonstrate that the program has been effective in both introducing genetic-specific challenges and assessing residents' clinical skills. It has helped trainees self-identify both strengths and further training needs. Pre- and postsurveys among the trainees show increased comfort levels in performing 5 of 12 genetic-related clinical tasks.We conclude that genetics OSCEs are an enriching educational tool. Merely providing trainees and practicing physicians with the latest scientific information is unlikely to prepare them for counseling patients about complex genetic issues. Developing proficiency requires focused practice and effective feedback.This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

Associations between sleep habits and mental health status and suicidality in a longitudinal survey of monozygotic twin adolescents.

PubMed

Matamura, Misato; Tochigi, Mamoru; Usami, Satoshi; Yonehara, Hiromi; Fukushima, Masako; Nishida, Atsushi; Togo, Fumiharu; Sasaki, Tsukasa

2014-06-01

Several epidemiological studies have indicated that there is a relationship between sleep habits, such as sleep duration, bedtime and bedtime regularity, and mental health status, including depression and anxiety in adolescents. However, it is still to be clarified whether the relationship is direct cause-and-effect or mediated by the influence of genetic and other traits, i.e. quasi-correlation. To examine this issue, we conducted a twin study using a total of 314 data for monozygotic twins from a longitudinal survey of sleep habits and mental health status conducted in a unified junior and senior high school (grades 7-12), located in Tokyo, Japan. Three-level hierarchical linear model analysis showed that both bedtime and sleep duration had significant associations with the Japanese version of the 12-item General Health Questionnaire (GHQ-12) score, suicidal thoughts and the experience of self-harm behaviours when genetic factors and shared environmental factors, which were completely shared between co-twins, were controlled for. These associations were statistically significant even after controlling for bedtime regularity, which was also associated significantly with the GHQ-12 score. These suggest that the associations between sleep habits and mental health status were still statistically significant after controlling for the influence of genetic and shared environmental factors of twins, and that there may be a direct cause-and-effect in the relationship in adolescents. Thus, late bedtime and short sleep duration could predict subsequent development of depression and anxiety, including suicidal or self-injury risk. This suggests that poor mental health status in adolescents might be improved by health education and intervention concerning sleep and lifestyle habits. © 2014 European Sleep Research Society.

Perceived stress is associated with increased rostral middle frontal gyrus cortical thickness: a family-based and discordant-sibling investigation.

PubMed

Michalski, L J; Demers, C H; Baranger, D A A; Barch, D M; Harms, M P; Burgess, G C; Bogdan, R

2017-11-01

Elevated stress perception and depression commonly co-occur, suggesting that they share a common neurobiology. Cortical thickness of the rostral middle frontal gyrus (RMFG), a region critical for executive function, has been associated with depression- and stress-related phenotypes. Here, we examined whether RMFG cortical thickness is associated with these phenotypes in a large family-based community sample. RMFG cortical thickness was estimated using FreeSurfer among participants (n = 879) who completed the ongoing Human Connectome Project. Depression-related phenotypes (i.e. sadness, positive affect) and perceived stress were assessed via self-report. After accounting for sex, age, ethnicity, average whole-brain cortical thickness, twin status and familial structure, RMFG thickness was positively associated with perceived stress and sadness and negatively associated with positive affect at small effect sizes (accounting for 0.2-2.4% of variance; p-fdr: 0.0051-0.1900). Perceived stress was uniquely associated with RMFG thickness after accounting for depression-related phenotypes. Further, among siblings discordant for perceived stress, those reporting higher perceived stress had increased RMFG thickness (P = 4 × 10 -7 ). Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive affect were all significantly heritable, with evidence of shared genetic and environmental contributions between self-report measures. Stress perception and depression share common genetic, environmental, and neural correlates. Variability in RMFG cortical thickness may play a role in stress-related depression, although effects may be small in magnitude. Prospective studies are required to examine whether variability in RMFG thickness may function as a risk factor for stress exposure and/or perception, and/or arises as a consequence of these phenotypes. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data

PubMed Central

Powell, Joseph E.; Henders, Anjali K.; McRae, Allan F.; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G.; Dermitzakis, Emmanouil T.; Gibson, Greg

2013-01-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted—in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects. PMID:23696747

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

PubMed

Powell, Joseph E; Henders, Anjali K; McRae, Allan F; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G; Dermitzakis, Emmanouil T; Gibson, Greg; Montgomery, Grant W; Visscher, Peter M

2013-05-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.

Inclusion of the fitness sharing technique in an evolutionary algorithm to analyze the fitness landscape of the genetic code adaptability.

PubMed

Santos, José; Monteagudo, Ángel

2017-03-27

The canonical code, although prevailing in complex genomes, is not universal. It was shown the canonical genetic code superior robustness compared to random codes, but it is not clearly determined how it evolved towards its current form. The error minimization theory considers the minimization of point mutation adverse effect as the main selection factor in the evolution of the code. We have used simulated evolution in a computer to search for optimized codes, which helps to obtain information about the optimization level of the canonical code in its evolution. A genetic algorithm searches for efficient codes in a fitness landscape that corresponds with the adaptability of possible hypothetical genetic codes. The lower the effects of errors or mutations in the codon bases of a hypothetical code, the more efficient or optimal is that code. The inclusion of the fitness sharing technique in the evolutionary algorithm allows the extent to which the canonical genetic code is in an area corresponding to a deep local minimum to be easily determined, even in the high dimensional spaces considered. The analyses show that the canonical code is not in a deep local minimum and that the fitness landscape is not a multimodal fitness landscape with deep and separated peaks. Moreover, the canonical code is clearly far away from the areas of higher fitness in the landscape. Given the non-presence of deep local minima in the landscape, although the code could evolve and different forces could shape its structure, the fitness landscape nature considered in the error minimization theory does not explain why the canonical code ended its evolution in a location which is not an area of a localized deep minimum of the huge fitness landscape.

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

DOE PAGES

McCluskey, Kevin; Baker, Scott E.

2017-02-17

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

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

McCluskey, Kevin; Baker, Scott E.

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

PubMed

Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

2013-09-01

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Somatoform Pain: A developmental theory and translational research review

PubMed Central

Landa, Alla; Peterson, Bradley S.; Fallon, Brian A.

2013-01-01

Somatoform pain is a highly prevalent, debilitating condition and a tremendous public health problem. Effective treatments for somatoform pain are urgently needed. The etiology of this condition is, however, still unknown. On the basis of a review of recent basic and clinical research, we propose one potential mechanisms of symptom formation in somatoform pain and a developmental theory of its pathogenesis. The emerging evidence from animal and human studies in developmental neurobiology, cognitive-affective neuroscience, psychoneuroimmunology, genetics, epigenetics, and clinical and treatment studies of somatoform pain all point to the existence of a shared physical and social pain neural system. Research findings also show that non-optimal early experiences interact with genetic predispositions to influence the development of this shared system and ability to regulate it in an effective way. Interpersonal affect regulation between infant and caregiver is crucial for the optimal development of these brain circuits. The aberrant development of this shared neural system during infancy, childhood and adolescence, therefore, may ultimately lead to an increased sensitivity to physical and social pain and to problems with their regulation in adulthood. The authors critically review translational research findings that support this theory and discuss its clinical and research implications. Specifically, the proposed theory and reviewed research suggest that psychotherapeutic and/or pharmacologic interventions that foster the development of affect regulation capacities in an interpersonal context will also serve to more effectively modulate aberrantly activated neural pain circuits and thus be of particular benefit in the treatment of somatoform pain. PMID:22929064

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.

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.

PubMed

Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N; Leppa, Virpi; Ramaswami, Gokul; Hartl, Chris; Schork, Andrew J; Appadurai, Vivek; Buil, Alfonso; Werge, Thomas M; Liu, Chunyu; White, Kevin P; Horvath, Steve; Geschwind, Daniel H

2018-02-09

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Heterogeneity in the development of proactive and reactive aggression in childhood: Common and specific genetic - environmental factors

PubMed Central

Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard Ernest; Boivin, Michel

2017-01-01

Background Few studies are grounded in a developmental framework to study proactive and reactive aggression. Furthermore, although distinctive correlates, predictors and outcomes have been highlighted, proactive and reactive aggression are substantially correlated. To our knowledge, no empirical study has examined the communality of genetic and environmental underpinning of the development of both subtypes of aggression. The current study investigated the communality and specificity of genetic-environmental factors related to heterogeneity in proactive and reactive aggression’s development throughout childhood. Methods Participants were 223 monozygotic and 332 dizygotic pairs. Teacher reports of aggression were obtained at 6, 7, 9, 10 and 12 years of age. Joint development of both phenotypes were analyzed through a multivariate latent growth curve model. Set point, differentiation, and genetic maturation/environmental modulation hypotheses were tested using a biometric decomposition of intercepts and slopes. Results Common genetic factors accounted for 64% of the total variation of proactive and reactive aggression’s intercepts. Two other sets of uncorrelated genetic factors accounted for reactive aggression’s intercept (17%) on the one hand, and for proactive (43%) and reactive (13%) aggression’s slopes on the other. Common shared environmental factors were associated with proactive aggression’s intercept (21%) and slope (26%) and uncorrelated shared environmental factors were also associated with reactive aggression’s slope (14%). Common nonshared environmental factors explained most of the remaining variability of proactive and reactive aggression slopes. Conclusions A genetic differentiation hypothesis common to both phenotypes was supported by common genetic factors associated with the developmental heterogeneity of proactive and reactive aggression in childhood. A genetic maturation hypothesis common to both phenotypes, albeit stronger for proactive aggression, was supported by common genetic factors associated with proactive and reactive aggression slopes. A shared environment set point hypothesis for proactive aggression was supported by shared environmental factors associated with proactive aggression baseline and slope. Although there are many common features to proactive and reactive aggression, the current research underscores the advantages of differentiating them when studying aggression. PMID:29211810

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register.

PubMed

Boomsma, D I; van Beijsterveldt, C E M; Hudziak, J J

2005-11-01

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.

Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder

PubMed Central

Cardno, Alastair G.

2014-01-01

There is substantial evidence for partial overlap of genetic influences on schizophrenia and bipolar disorder, with family, twin, and adoption studies showing a genetic correlation between the disorders of around 0.6. Results of genome-wide association studies are consistent with commonly occurring genetic risk variants, contributing to both the shared and nonshared aspects, while studies of large, rare chromosomal structural variants, particularly copy number variants, show a stronger influence on schizophrenia than bipolar disorder to date. Schizoaffective disorder has been less investigated but shows substantial familial overlap with both schizophrenia and bipolar disorder. A twin analysis is consistent with genetic influences on schizoaffective episodes being entirely shared with genetic influences on schizophrenic and manic episodes, while association studies suggest the possibility of some relatively specific genetic influences on broadly defined schizoaffective disorder, bipolar subtype. Further insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant. PMID:24567502

Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

PubMed Central

Tucker-Drob, Elliot M.; Briley, Daniel A.

2014-01-01

The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress.

PubMed

Wolf, Erika J; Miller, Mark W; Sullivan, Danielle R; Amstadter, Ananda B; Mitchell, Karen S; Goldberg, Jack; Magruder, Kathryn M

2018-02-01

To examine shared genetic and environmental risk factors across PTSD symptoms and resilience. Classical twin study of 2010-2012 survey data conducted among 3,318 male twin pairs in the Vietnam Era Twin Registry. Analyses included: (a) estimates of genetic and environmental influences on PTSD symptom severity (as measured by the PTSD Checklist) and resilience (assessed with the Connor-Davidson Resilience Scale-10); (b) development of a latent model of traumatic stress, spanning both PTSD and resilience; and (c) estimates of genetic and environmental influences on this spectrum. The heritability of PTSD was 49% and of resilience was 25%. PTSD and resilience were correlated at r = -.59, and 59% of this correlation was attributable to a single genetic factor, whereas the remainder was due to a single non-shared environment factor. Resilience was also influenced by common and unique environmental factors not shared with PTSD, but there was no genetic factor specific to resilience. Confirmatory factor analysis supported the Development of a revised phenotype reflecting the broader dimension of traumatic stress, with biometric models suggesting increased heritability (66%) of this spectrum compared to PTSD or resilience individually. Genetic factors contribute to a single spectrum of traumatic stress reflecting resilience at one end and high symptom severity at the other. This carries implications for phenotype refinement in the search for molecular genetic markers of trauma-related psychopathology. Rather than focusing only on genetic risk for PTSD, molecular genetics research may benefit from evaluation of the broader spectrum of traumatic stress. © 2017 Wiley Periodicals, Inc.

Mammographic breast density and breast cancer: evidence of a shared genetic basis.

PubMed

Varghese, Jajini S; Thompson, Deborah J; Michailidou, Kyriaki; Lindström, Sara; Turnbull, Clare; Brown, Judith; Leyland, Jean; Warren, Ruth M L; Luben, Robert N; Loos, Ruth J; Wareham, Nicholas J; Rommens, Johanna; Paterson, Andrew D; Martin, Lisa J; Vachon, Celine M; Scott, Christopher G; Atkinson, Elizabeth J; Couch, Fergus J; Apicella, Carmel; Southey, Melissa C; Stone, Jennifer; Li, Jingmei; Eriksson, Louise; Czene, Kamila; Boyd, Norman F; Hall, Per; Hopper, John L; Tamimi, Rulla M; Rahman, Nazneen; Easton, Douglas F

2012-03-15

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of single-nucleotide polymorphisms (SNP) were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case-control status as the outcome. This analysis was repeated using 10 different cutoff points for the most significant density SNPs (1%-10% representing 5,222-50,899 SNPs). Permutation analysis was also conducted across all 10 cutoff points. The association between risk score and breast cancer was significant for all cutoff points from 3% to 10% of top density SNPs, being most significant for the 6% (2-sided P = 0.002) to 10% (P = 0.001) cutoff points (overall permutation P = 0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR = 1.31; 95% confidence interval (CI), 1.08-1.59] compared with women in the bottom 10%. Together, our results show that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants.

Mammographic breast density and breast cancer: evidence of a shared genetic basis

PubMed Central

Varghese, Jajini S; Thompson, Deborah J; Michailidou, Kyriaki; Lindström, Sara; Turnbull, Clare; Brown, Judith; Leyland, Jean; Warren, Ruth ML; Luben, Robert N; Loos, Ruth J; Wareham, Nicholas J; Rommens, Johanna; Paterson, Andrew D; Martin, Lisa J; Vachon, Celine M; Scott, Christopher G; Atkinson, Elizabeth J; Couch, Fergus J; Apicella, Carmel; Southey, Melissa C; Stone, Jennifer; Li, Jingmei; Eriksson, Louise; Czene, Kamila; Boyd, Norman F; Hall, Per; Hopper, John L; Tamimi, Rulla M; Rahman, Nazneen; Easton, Douglas F

2012-01-01

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3628 breast cancer cases and 5190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of SNPs were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case-control status as the outcome. This analysis was repeated using ten different cut-offs for the most significant density SNPs (1-10% representing 5,222-50,899 SNPs). Permutation analysis was also performed across all 10 cut-offs. The association between risk score and breast cancer was significant for all cut-offs from 3-10% of top density SNPs, being most significant for the 6% (2-sided P=0.002) to 10% (P=0.001) cut-offs (overall permutation P=0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR= 1.31 (95%CI 1.08-1.59)] compared to women in the bottom 10%. Together, our results demonstrate that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants. PMID:22266113

Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

PubMed Central

Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

2013-01-01

Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

Are obesity and body fat distribution associated with low back pain in women? A population-based study of 1128 Spanish twins.

PubMed

Dario, Amabile B; Ferreira, Manuela L; Refshauge, Kathryn; Sánchez-Romera, Juan F; Luque-Suarez, Alejandro; Hopper, John L; Ordoñana, Juan R; Ferreira, Paulo H

2016-04-01

To investigate the relationship between different measures of obesity and chronic low back pain (LBP) using a within-pair twin case-control design that adjusts for genetics and early shared environment. A cross-sectional association between lifetime prevalence of chronic LBP and different measures of obesity (body mass index-BMI; percent body fat; waist circumference; waist-hip ratio) was investigated in 1128 female twins in three stages: (i) total sample analysis; (ii) within-pair case-control analysis for monozygotic (MZ) and dizygotic (DZ) twins together; (iii) within-pair case-control analysis separated by DZ and MZ. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. BMI (OR 1.12; 95% CI 1.02-1.26) and percent body fat (OR 1.15; 95% CI 1.01-1.32) were weakly associated with lifetime prevalence of chronic LBP in the total sample analysis but were absent when shared environment and genetic factors were adjusted for using the within-pair case-control analysis. Greater waist-hip ratios were associated with smaller prevalence estimates of chronic LBP in the within-pair case-control analysis with both MZ and DZ twins (OR 0.67; 95% CI 0.47-0.94). However, this association did not remain after the full adjustment for genetic factors in the MZ within-pair case-control analysis. BMI, percent of fat mass and greater depositions of fat and mass around the hips are associated with increases in chronic LBP prevalence in women but these associations are small and appear to be confounded by the effects of genetics and early shared environment. Therefore, our results do not support a causal direct relationship between obesity and chronic LBP.

Minor Allele Frequency Changes the Nature of Genotype by Environment Interactions.

PubMed

Verhulst, Brad; Neale, Michael C

2016-09-01

In the classical twin study, phenotypic variation is often partitioned into additive genetic (A), common (C) and specific environment (E) components. From genetical theory, the outcome of genotype by environment interaction is expected to inflate A when the interacting factor is shared (i.e., C) between the members of a twin pair. We show that estimates of both A and C can be inflated. When the shared interacting factor changes the size of the difference between homozygotes' means, the expected sibling or DZ twin correlation is .5 if and only if the minor allele frequency (MAF) is .5; otherwise the expected DZ correlation is greater than this value, consistent (and confounded) with some additional effect of C. This result is considered in the light of the distribution of minor allele frequencies for polygenic traits. Also discussed is whether such interactions take place at the locus level or affect an aggregated biological structure or system. Interactions with structures or endophenotypes that result from the aggregated effects of many loci will generally emerge as part of the A estimate.

Host Genetics and Environment Drive Divergent Responses of Two Resource Sharing Gall-Formers on Norway Spruce: A Common Garden Analysis.

PubMed

Axelsson, E Petter; Iason, Glenn R; Julkunen-Tiitto, Riitta; Whitham, Thomas G

2015-01-01

A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp.) that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L.) support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch). Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members respond to host genetics supports our hypothesis that the canopies of Norway spruce differ in their community phenotypes.

Medical Genetics and the First Studies of the Genetics of Populations in Mexico

PubMed Central

Barahona, Ana

2016-01-01

Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén’s studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl’s studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker’s studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. PMID:27601615

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

PubMed

Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

2017-11-02

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Environment dominates over host genetics in shaping human gut microbiota.

PubMed

Rothschild, Daphna; Weissbrod, Omer; Barkan, Elad; Kurilshikov, Alexander; Korem, Tal; Zeevi, David; Costea, Paul I; Godneva, Anastasia; Kalka, Iris N; Bar, Noam; Shilo, Smadar; Lador, Dar; Vila, Arnau Vich; Zmora, Niv; Pevsner-Fischer, Meirav; Israeli, David; Kosower, Noa; Malka, Gal; Wolf, Bat Chen; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Weinberger, Adina; Halpern, Zamir; Carmi, Shai; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Elinav, Eran; Segal, Eran

2018-03-08

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Genetic and environmental influences on individual differences in emotion regulation and its relation to working memory in toddlerhood.

PubMed

Wang, Manjie; Saudino, Kimberly J

2013-12-01

This is the first study to explore genetic and environmental contributions to individual differences in emotion regulation in toddlers, and the first to examine the genetic and environmental etiology underlying the association between emotion regulation and working memory. In a sample of 304 same-sex twin pairs (140 MZ, 164 DZ) at age 3, emotion regulation was assessed using the Behavior Rating Scale of the Bayley Scales of Infant Development (BRS; Bayley, 1993), and working memory was measured by the visually cued recall (VCR) task (Zelazo, Jacques, Burack, & Frye, 2002) and several memory tasks from the Mental Scale of the BSID. Based on model-fitting analyses, both emotion regulation and working memory were significantly influenced by genetic and nonshared environmental factors. Shared environmental effects were significant for working memory, but not for emotion regulation. Only genetic factors significantly contributed to the covariation between emotion regulation and working memory.

Cardiovascular Disease, Psychosocial Factors, and Genetics: The Case of Depression

PubMed Central

Mulle, Jennifer Gladys; Vaccarino, Viola

2013-01-01

Psychosocial factors are associated with cardiovascular disease, but little is known about the role of genetics in this relationship. Focusing on the well-studied phenotype of depression, current data show that there are shared genetic factors that may give rise to both depression and CVD, and these genetic risks appear to be modified by gender. This pleiotropic effect suggests that a single pathway, when perturbed, gives rise to the dual phenotypes of CVD and depression. The data also suggest that women contribute disproportionately to the depression-CVD comorbidity, and this unbalanced contribution is attributable, in part, to genetic factors. While the underlying biology behind this relationship is unclear, recent data support contributions from inflammatory or serotonergic pathways toward the comorbidity between CVD and depression. Even without knowledge of a specific mechanism, epidemiological observations offer new directions to explain the relationship between depression and CVD that have both research and clinical applications. PMID:23621965

Genetic and Environmental Influences on Individual Differences in Emotion Regulation and Its Relation to Working Memory in Toddlerhood

PubMed Central

Wang, Manjie; Saudino, Kimberly J.

2014-01-01

This is the first study to explore genetic and environmental contributions to individual differences in emotion regulation in toddlers, and the first to examine the genetic and environmental etiology underlying the association between emotion regulation and working memory. In a sample of 304 same-sex twin pairs (140 MZ, 164 DZ) at age 3, emotion regulation was assessed using the Behavior Rating Scale of the Bayley Scales of Infant Development (BRS; Bayley, 1993), and working memory was measured by the visually cued recall (VCR) task (Zelazo et al., 2002) and several memory tasks from the Mental Scale of BSID. Based on model-fitting analyses, both emotion regulation and working memory were significantly influenced by genetic and nonshared environmental factors. Shared environmental effects were significant for working memory, but not for emotion regulation. Only genetic factors significantly contributed to the covariation between emotion regulation and working memory. PMID:24098922

Genetic and environmental variance in content dimensions of the MMPI.

PubMed

Rose, R J

1988-08-01

To evaluate genetic and environmental variance in the Minnesota Multiphasic Personality Inventory (MMPI), I studied nine factor scales identified in the first item factor analysis of normal adult MMPIs in a sample of 820 adolescent and young adult co-twins. Conventional twin comparisons documented heritable variance in six of the nine MMPI factors (Neuroticism, Psychoticism, Extraversion, Somatic Complaints, Inadequacy, and Cynicism), whereas significant influence from shared environmental experience was found for four factors (Masculinity versus Femininity, Extraversion, Religious Orthodoxy, and Intellectual Interests). Genetic variance in the nine factors was more evident in results from twin sisters than those of twin brothers, and a developmental-genetic analysis, using hierarchical multiple regressions of double-entry matrixes of the twins' raw data, revealed that in four MMPI factor scales, genetic effects were significantly modulated by age or gender or their interaction during the developmental period from early adolescence to early adulthood.

Exploring how symptoms of attention-deficit/hyperactivity disorder are related to reading and mathematics performance: general genes, general environments.

PubMed

Hart, Sara A; Petrill, Stephen A; Willcutt, Erik; Thompson, Lee A; Schatschneider, Christopher; Deater-Deckard, Kirby; Cutting, Laurie E

2010-11-01

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.

Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

PubMed Central

Brandi, Giovanni; Farioli, Andrea; Astolfi, Annalisa; Biasco, Guido; Tavolari, Simona

2015-01-01

Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID:26142706

Sex differences in genetic and environmental influences on percent body fatness and physical activity.

PubMed

White, Erin; Slane, Jennifer D; Klump, Kelly L; Burt, S Alexandra; Pivarnik, Jim

2014-08-01

Knowing the extent to which genetic and environmental factors influence percent body fatness (%Fat) and physical activity (PA) would be beneficial, since both are tightly correlated with future health outcomes. Thus, the purpose was to evaluate sex differences in genetic and environmental influences on %Fat and physical activity behavior in male and female adolescent twins. Subjects were adolescent (age range 8.3 to 16.6 yr) twins. %Fat (n = 518 twins) was assessed by bioelectrical impedance analysis (BIA) and PA (n = 296 twins) was measured using 3-Day PA Recall. Each activity was converted to total MET-minutes. Univariate twin models were used to examine sex differences in genetic and environmental factors influencing %Fat and PA. %Fat was influenced by genetic effects in both boys and girls (88% and 90%, respectively), with slightly higher heritability estimates for girls. PA was influenced solely by environmental effects for both sexes with higher shared environmental influences in boys (66%) and higher nonshared effects in girls (67%). When developing interventions to increase PA in adolescents, it is important to consider the environment in which it takes place as it is the primary contributor to PA levels.

The Genetic Overlap of Attention-Deficit/Hyperactivity Disorder and Autistic-like Traits: an Investigation of Individual Symptom Scales and Cognitive markers.

PubMed

Pinto, Rebecca; Rijsdijk, Fruhling; Ronald, Angelica; Asherson, Philip; Kuntsi, Jonna

2016-02-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) frequently co-occur. However, due to previous exclusionary diagnostic criteria, little is known about the underlying causes of this covariation. Twin studies assessing ADHD symptoms and autistic-like traits (ALTs) suggest substantial genetic overlap, but have largely failed to take into account the genetic heterogeneity of symptom subscales. This study aimed to clarify the phenotypic and genetic relations between ADHD and ASD by distinguishing between symptom subscales that characterise the two disorders. Moreover, we aimed to investigate whether ADHD-related cognitive impairments show a relationship with ALT symptom subscales; and whether potential shared cognitive impairments underlie the genetic risk shared between the ADHD and ALT symptoms. Multivariate structural equation modelling was conducted on a population-based sample of 1312 twins aged 7-10. Social-communication ALTs correlated moderately with both ADHD symptom domains (phenotypic correlations around 0.30) and showed substantial genetic overlap with both inattention and hyperactivity-impulsivity (genetic correlation = 0.52 and 0.44, respectively). In addition to previously reported associations with ADHD traits, reaction time variability (RTV) showed significant phenotypic (0.18) and genetic (0.32) association with social-communication ALTs. RTV captured a significant proportion (24 %) of the genetic influences shared between inattention and social-communication ALTs. Our findings suggest that social-communication ALTs underlie the previously observed phenotypic and genetic covariation between ALTs and ADHD symptoms. RTV is not specific to ADHD symptoms, but is also associated with social-communication ALTs and can, in part, contribute to an explanation of the co-occurrence of ASD and ADHD.

Common genetic architecture underlying young children's food fussiness and liking for vegetables and fruit.

PubMed

Fildes, Alison; van Jaarsveld, Cornelia H M; Cooke, Lucy; Wardle, Jane; Llewellyn, Clare H

2016-04-01

Food fussiness (FF) is common in early childhood and is often associated with the rejection of nutrient-dense foods such as vegetables and fruit. FF and liking for vegetables and fruit are likely all heritable phenotypes; the genetic influence underlying FF may explain the observed genetic influence on liking for vegetables and fruit. Twin analyses make it possible to get a broad-based estimate of the extent of the shared genetic influence that underlies these traits. We quantified the extent of the shared genetic influence that underlies FF and liking for vegetables and fruit in early childhood with the use of a twin design. Data were from the Gemini cohort, which is a population-based sample of twins born in England and Wales in 2007. Parents of 3-y-old twins (n= 1330 pairs) completed questionnaire measures of their children's food preferences (liking for vegetables and fruit) and the FF scale from the Children's Eating Behavior Questionnaire. Multivariate quantitative genetic modeling was used to estimate common genetic influences that underlie FF and liking for vegetables and fruit. Genetic correlations were significant and moderate to large in size between FF and liking for both vegetables (-0.65) and fruit (-0.43), which indicated that a substantial proportion of the genes that influence FF also influence liking. Common genes that underlie FF and liking for vegetables and fruit largely explained the observed phenotypic correlations between them (68-70%). FF and liking for fruit and vegetables in young children share a large proportion of common genetic factors. The genetic influence on FF may determine why fussy children typically reject fruit and vegetables.

Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap.

PubMed

Terao, Chikashi; Matsumura, Takayoshi; Yoshifuji, Hajime; Kirino, Yohei; Maejima, Yasuhiro; Nakaoka, Yoshikazu; Takahashi, Meiko; Amiya, Eisuke; Tamura, Natsuko; Nakajima, Toshiki; Origuchi, Tomoki; Horita, Tetsuya; Matsukura, Mitsuru; Kochi, Yuta; Ogimoto, Akiyoshi; Yamamoto, Motohisa; Takahashi, Hiroki; Nakayamada, Shingo; Saito, Kazuyoshi; Wada, Yoko; Narita, Ichiei; Kawaguchi, Yasushi; Yamanaka, Hisashi; Ohmura, Koichiro; Atsumi, Tatsuya; Tanemoto, Kazuo; Miyata, Tetsuro; Kuwana, Masataka; Komuro, Issei; Tabara, Yasuharu; Ueda, Atsuhisa; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

2015-05-01

Takayasu arteritis (TAK) is a systemic vasculitis affecting large arteries and large branches of the aorta. Ulcerative colitis (UC) is a prevalent autoimmune colitis. Since TAK and UC share HLA-B*52:01 and IL12B as genetic determinants, and since there are case reports of the co-occurrence of these diseases, we hypothesized that UC is a common complication of TAK. We undertook this study to perform a large-scale analysis of TAK, both to evaluate the prevalence of concurrent cases of TAK and UC and to identify and estimate susceptibility genes shared between the 2 diseases. We analyzed a total of 470 consecutive patients with TAK from 14 institutions. We characterized patients with TAK and UC by analyzing clinical manifestations and genetic components. Genetic overlapping of TAK and UC was evaluated with the use of UC susceptibility single-nucleotide polymorphisms by comparing risk directions and effect sizes between susceptibility to the 2 diseases. Thirty of 470 patients with TAK had UC (6.4% [95% confidence interval 4.3-9.0]). This percentage was strikingly higher than that expected from the prevalence of UC in Japan. Patients with TAK complicated with UC developed TAK at an earlier stage of life (P = 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P = 1.0 × 10(-5) ) (odds ratio 12.14 [95% confidence interval 2.96-107.23]). The 110 non-HLA markers of susceptibility to UC significantly displayed common risk directions with susceptibility to TAK (P = 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 × 10(-10) ). UC is a major complication of TAK. These 2 diseases share a significant proportion of their genetic background, and HLA-B*52:01 may play a central role in their co-occurrence. © 2015, American College of Rheumatology.

Common genetic variants explain the majority of the correlation between height and intelligence: the generation Scotland study.

PubMed

Marioni, Riccardo E; Batty, G David; Hayward, Caroline; Kerr, Shona M; Campbell, Archie; Hocking, Lynne J; Porteous, David J; Visscher, Peter M; Deary, Ian J

2014-03-01

Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49-63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a bivariate heritability estimate of 0.71. Understanding the molecular basis of the correlation between height and intelligence may help explain any shared role in determining health outcomes. This study identified a modest genetic correlation between height and intelligence with the majority of the phenotypic correlation being explained by shared genetic influences.

Moderation of genetic factors by parental divorce in adolescents' evaluations of family functioning and subjective wellbeing.

PubMed

van der Aa, Niels; Boomsma, Dorret I; Rebollo-Mesa, Irene; Hudziak, James J; Bartels, Meike

2010-04-01

Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.

A social relations model of observed family negativity and positivity using a genetically informative sample.

PubMed

Rasbash, Jon; Jenkins, Jennifer; O'Connor, Thomas G; Tackett, Jennifer; Reiss, David

2011-03-01

The goal of this study was to investigate individual and relationship influences on expressions of negativity and positivity in families. Parents and adolescents were observed in a round-robin design in a sample of 687 families. Data were analyzed using a multilevel social relations model. In addition, genetic contributions were estimated for actor effects. Children showed higher mean levels of negativity and lower mean levels of positivity as actors than did parents. Mothers were found to express and elicit higher mean levels of positivity and negativity than fathers. Actor effects were much stronger than partner effects, accounting for between 18%-39% of the variance depending on the actor and the outcome. Genetic (35%) and shared environmental (19%) influences explained a substantial proportion of the actor effect variance for negativity. Dyadic reciprocities were lowest in dyads with a high power differential (i.e., parent-child dyads) and highest for dyads with equal power (sibling and marital dyads). (c) 2011 APA, all rights reserved

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

PubMed Central

Zeng, Y.; Yin, T.; Brügemann, K.

2018-01-01

Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle. PMID:29608619

The death(s) of close friends and family moderate genetic influences on symptoms of major depressive disorder in adolescents.

PubMed

Gheyara, S; Klump, K L; McGue, M; Iacono, W G; Burt, S A

2011-04-01

Prior work has suggested that genetic influences on major depressive disorder (MDD) may be activated by the experience of negative life events. However, it is unclear whether these results persist when controlling for the possibility of confounding active gene-environment correlations (rGE). We examined a sample of 1230 adopted and biological siblings between the ages of 10 and 20 years from the Sibling Interaction and Behavior Study. MDD was measured via a lifetime DSM-IV symptom count. Number of deaths experienced served as our environmental risk experience. Because this variable is largely independent of the individual's choices/behaviors, we were able to examine gene-environment interactions while circumventing possible rGE confounds. Biometric analyses revealed pronounced linear increases in the magnitude of genetic influences on symptoms of MDD with the number of deaths experienced, such that genetic influences were estimated to be near-zero for those who had experienced no deaths but were quite large in those who had experienced two or more deaths (i.e. accounting for roughly two-thirds of the phenotypic variance). By contrast, shared and non-shared environmental influences on symptoms of MDD were not meaningfully moderated by the number of deaths experienced. Such results constructively replicate prior findings of genetic moderation of depressive symptoms by negative life events, thereby suggesting that this effect is not a function of active rGE confounds. Our findings are thus consistent with the notion that exposure to specific negative life events may serve to activate genetic risk for depression during adolescence.

The effects of dog breed development on genetic diversity and the relative influences of performance and conformation breeding.

PubMed

Pedersen, N; Liu, H; Theilen, G; Sacks, B

2013-06-01

Genetic diversity was compared among eight dog breeds selected primarily for conformation (Standard Poodle, Italian Greyhound and show English Setter), conformation and performance (Brittany), predominantly performance (German Shorthaired and Wirehaired Pointers) or solely performance (field English Setter and Red Setter). Modern village dogs, which better reflect ancestral genetic diversity, were used as the standard. Four to seven maternal and one to two Y haplotypes were found per breed, with one usually dominant. Diversity of maternal haplotypes was greatest in village dogs, intermediate in performance breeds and lowest in conformation breeds. Maternal haplotype sharing occurred across all breeds, while Y haplotypes were more breed specific. Almost all paternal haplotypes were identified among village dogs, with the exception of the dominant Y haplotype in Brittanys, which has not been identified heretofore. The highest heterozygosity based on 24 autosomal microsatellites was found in village dogs and the lowest in conformation (show) breeds. Principal coordinate analysis indicated that conformation-type breeds were distinct from breeds heavily used for performance, the latter clustering more closely with village dogs. The Brittany, a well-established dual show and field breed, was also genetically intermediate between the conformation and performance breeds. The number of DLA-DRB1 alleles varied from 3 to 10 per breed with extensive sharing. SNPs across the wider DLA region were more frequently homozygous in all pure breeds than in village dogs. Compared with their village dog relatives, all modern breed dogs exhibit reduced genetic diversity. Genetic diversity was even more reduced among breeds under selection for show/conformation. © 2012 Blackwell Verlag GmbH.

Sleep Duration and Depressive Symptoms: A Gene-Environment Interaction

PubMed Central

Watson, Nathaniel F.; Harden, Kathryn Paige; Buchwald, Dedra; Vitiello, Michael V.; Pack, Allan I.; Strachan, Eric; Goldberg, Jack

2014-01-01

Objective: We used quantitative genetic models to assess whether sleep duration modifies genetic and environmental influences on depressive symptoms. Method: Participants were 1,788 adult twins from 894 same-sex twin pairs (192 male and 412 female monozygotic [MZ] pairs, and 81 male and 209 female dizygotic [DZ] pairs] from the University of Washington Twin Registry. Participants self-reported habitual sleep duration and depressive symptoms. Data were analyzed using quantitative genetic interaction models, which allowed the magnitude of additive genetic, shared environmental, and non-shared environmental influences on depressive symptoms to vary with sleep duration. Results: Within MZ twin pairs, the twin who reported longer sleep duration reported fewer depressive symptoms (ec = -0.17, SE = 0.06, P < 0.05). There was a significant gene × sleep duration interaction effect on depressive symptoms (a'c = 0.23, SE = 0.08, P < 0.05), with the interaction occurring on genetic influences that are common to both sleep duration and depressive symptoms. Among individuals with sleep duration within the normal range (7-8.9 h/night), the total heritability (h2) of depressive symptoms was approximately 27%. However, among individuals with sleep duration within the low (< 7 h/night) or high (≥ 9 h/night) range, increased genetic influence on depressive symptoms was observed, particularly at sleep duration extremes (5 h/night: h2 = 53%; 10 h/night: h2 = 49%). Conclusion: Genetic contributions to depressive symptoms increase at both short and long sleep durations. Citation: Watson NF; Harden KP; Buchwald D; Vitiello MV; Pack AI; Stachan E; Goldberg J. Sleep duration and depressive symptoms: a gene-environment interaction. SLEEP 2014;37(2):351-358. PMID:24497663

Added value measures in education show genetic as well as environmental influence.

PubMed

Haworth, Claire M A; Asbury, Kathryn; Dale, Philip S; Plomin, Robert

2011-02-02

Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities.

An overview of human genetic privacy

PubMed Central

Shi, Xinghua; Wu, Xintao

2016-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. PMID:27626905

The complexity of personality: advantages of a genetically sensitive multi-group design.

PubMed

Hahn, Elisabeth; Spinath, Frank M; Siedler, Thomas; Wagner, Gert G; Schupp, Jürgen; Kandler, Christian

2012-03-01

Findings from many behavioral genetic studies utilizing the classical twin design suggest that genetic and non-shared environmental effects play a significant role in human personality traits. This study focuses on the methodological advantages of extending the sampling frame to include multiple dyads of relatives. We investigated the sensitivity of heritability estimates to the inclusion of sibling pairs, mother-child pairs and grandparent-grandchild pairs from the German Socio-Economic Panel Study in addition to a classical German twin sample consisting of monozygotic- and dizygotic twins. The resulting dataset contained 1.308 pairs, including 202 monozygotic and 147 dizygotic twin pairs, along with 419 sibling pairs, 438 mother-child dyads, and 102 grandparent-child dyads. This genetically sensitive multi-group design allowed the simultaneous testing of additive and non-additive genetic, common and specific environmental effects, including cultural transmission and twin-specific environmental influences. Using manifest and latent modeling of phenotypes (i.e., controlling for measurement error), we compare results from the extended sample with those from the twin sample alone and discuss implications for future research.

Cohabiting family members share microbiota with one another and with their dogs.

PubMed

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-04-16

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more 'skin' microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI:http://dx.doi.org/10.7554/eLife.00458.001.

Cohabiting family members share microbiota with one another and with their dogs

PubMed Central

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-01-01

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more ‘skin’ microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI: http://dx.doi.org/10.7554/eLife.00458.001 PMID:23599893

Twins and virtual twins: Do genetic (as well as experiential) factors affect developmental risks?

PubMed

Segal, Nancy L; Tan, Tony Xing; Graham, Jamie L

2015-08-01

Factors underlying developmental delays and psychosocial risks are of interest to international adoption communities. The current study administered a Pre-Adoption Adversity (PAA) Questionnaire to mostly American parents raising (a) adopted Chinese twins or (b) same-age unrelated adopted siblings. A goal was to replicate earlier analyses of pre-adoption adversity/adjustment among adopted preschool-age Chinese girls. A second goal was to conduct genetic analyses of four content areas (Developmental Delays at Adoption, Initial Adaptation to Adoption, Crying/Clinging, and Refusal/Avoidance) derived from the PAA Questionnaire. A key finding was that age at adoption added less than other predictors to adoptees' externalizing and internalizing behaviors. Family factors (e.g., parental education) contributed significantly to behavioral outcomes among the adopted Chinese twins. Genetic effects were indicated for all four content areas, with shared environmental effects evident for Developmental Delays at Adoption and Crying/Clinging. Future investigators should consider incorporating genetically sensitive designs into developmental research programs. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimating the Sex-Specific Effects of Genes on Facial Attractiveness and Sexual Dimorphism

PubMed Central

Purkey, Alicia M.; Grebe, Nicholas M.; Carey, Gregory; Garver-Apgar, Christine E.; Bates, Timothy C.; Arden, Rosalind; Hewitt, John K.; Medland, Sarah E.; Martin, Nicholas G.; Zietsch, Brendan P.; Keller, Matthew C.

2014-01-01

Human facial attractiveness and facial sexual dimorphism (masculinity–femininity) are important facets of mate choice and are hypothesized to honestly advertise genetic quality. However, it is unclear whether genes influencing facial attractiveness and masculinity–femininity have similar, opposing, or independent effects across sex, and the heritability of these phenotypes is poorly characterized. To investigate these issues, we assessed facial attractiveness and facial masculinity–femininity in the largest genetically informative sample (n = 1,580 same- and opposite-sex twin pairs and siblings) to assess these questions to date. The heritability was ~0.50–0.70 for attractiveness and ~0.40–0.50 for facial masculinity– femininity, indicating that, despite ostensible selection on genes influencing these traits, substantial genetic variation persists in both. Importantly, we found evidence for intralocus sexual conflict, whereby alleles that increase masculinity in males have the same effect in females. Additionally, genetic influences on attractiveness were shared across the sexes, suggesting that attractive fathers tend to have attractive daughters and attractive mothers tend to have attractive sons. PMID:24213680

A Twin Study of Normative Personality and DSM-IV Personality Disorder Criterion Counts: Evidence for Separate Genetic Influences.

PubMed

Czajkowski, Nikolai; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Neale, Michael C; Knudsen, Gun Peggy; Gillespie, Nathan A; Røysamb, Espen; Tambs, Kristian; Reichborn-Kjennerud, Ted

2018-03-21

Both normative personality and DSM-IV personality disorders have been found to be heritable. However, there is limited knowledge about the extent to which the genetic and environmental influences underlying DSM personality disorders are shared with those of normative personality. The aims of this study were to assess the phenotypic similarity between normative and pathological personality and to investigate the extent to which genetic and environmental influences underlying individual differences in normative personality account for symptom variance across DSM-IV personality disorders. A large population-based sample of adult twins was assessed for DSM-IV personality disorder criteria with structured interviews at two waves spanning a 10-year interval. At the second assessment, participants also completed the Big Five Inventory, a self-report instrument assessing the five-factor normative personality model. The proportion of genetic and environmental liabilities unique to the individual personality disorder measures, and hence not shared with the five Big Five Inventory domains, were estimated by means of multivariate Cholesky twin decompositions. The median percentage of genetic liability to the 10 DSM-IV personality disorders assessed at wave 1 that was not shared with the Big Five domains was 64%, whereas for the six personality disorders that were assessed concurrently at wave 2, the median was 39%. Conversely, the median proportions of unique environmental liability in the personality disorders for wave 1 and wave 2 were 97% and 96%, respectively. The results indicate that a moderate-to-sizable proportion of the genetic influence underlying DSM-IV personality disorders is not shared with the domain constructs of the Big Five model of normative personality. Caution should be exercised in assuming that normative personality measures can serve as proxies for DSM personality disorders when investigating the etiology of these disorders.

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry

PubMed Central

Davidson, Natalie R.; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L.; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. PMID:27010569

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry.

PubMed

Waldman, Yedael Y; Biddanda, Arjun; Davidson, Natalie R; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19-33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so.

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.

Vibrio chromosomes share common history.

PubMed

Kirkup, Benjamin C; Chang, LeeAnn; Chang, Sarah; Gevers, Dirk; Polz, Martin F

2010-05-10

While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II) were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA) for one chromosome to be applied equally to both chromosomes.

Genetic Architecture Promotes the Evolution and Maintenance of Cooperation

PubMed Central

Frénoy, Antoine; Taddei, François; Misevic, Dusan

2013-01-01

When cooperation has a direct cost and an indirect benefit, a selfish behavior is more likely to be selected for than an altruistic one. Kin and group selection do provide evolutionary explanations for the stability of cooperation in nature, but we still lack the full understanding of the genomic mechanisms that can prevent cheater invasion. In our study we used Aevol, an agent-based, in silico genomic platform to evolve populations of digital organisms that compete, reproduce, and cooperate by secreting a public good for tens of thousands of generations. We found that cooperating individuals may share a phenotype, defined as the amount of public good produced, but have very different abilities to resist cheater invasion. To understand the underlying genetic differences between cooperator types, we performed bio-inspired genomics analyses of our digital organisms by recording and comparing the locations of metabolic and secretion genes, as well as the relevant promoters and terminators. Association between metabolic and secretion genes (promoter sharing, overlap via frame shift or sense-antisense encoding) was characteristic for populations with robust cooperation and was more likely to evolve when secretion was costly. In mutational analysis experiments, we demonstrated the potential evolutionary consequences of the genetic association by performing a large number of mutations and measuring their phenotypic and fitness effects. The non-cooperating mutants arising from the individuals with genetic association were more likely to have metabolic deleterious mutations that eventually lead to selection eliminating such mutants from the population due to the accompanying fitness decrease. Effectively, cooperation evolved to be protected and robust to mutations through entangled genetic architecture. Our results confirm the importance of second-order selection on evolutionary outcomes, uncover an important genetic mechanism for the evolution and maintenance of cooperation, and suggest promising methods for preventing gene loss in synthetically engineered organisms. PMID:24278000

Learning abilities and disabilities: generalist genes in early adolescence.

PubMed

Davis, Oliver S P; Haworth, Claire M A; Plomin, Robert

2009-01-01

The new view of cognitive neuropsychology that considers not just case studies of rare severe disorders but also common disorders, as well as normal variation and quantitative traits, is more amenable to recent advances in molecular genetics, such as genome-wide association studies, and advances in quantitative genetics, such as multivariate genetic analysis. A surprising finding emerging from multivariate quantitative genetic studies across diverse learning abilities is that most genetic influences are shared: they are "generalist", rather than "specialist". We exploited widespread access to inexpensive and fast Internet connections in the United Kingdom to assess over 5000 pairs of 12-year-old twins from the Twins Early Development Study (TEDS) on four distinct batteries: reading, mathematics, general cognitive ability (g) and, for the first time, language. Genetic correlations remain high among all of the measured abilities, with language as highly correlated genetically with g as reading and mathematics. Despite developmental upheaval, generalist genes remain important into early adolescence, suggesting optimal strategies for molecular genetic studies seeking to identify the genes of small effect that influence learning abilities and disabilities.

Shared environmental influences on personality: A combined twin and adoption approach

PubMed Central

Matteson, Lindsay K.; McGue, Matt; Iacono, William G.

2013-01-01

In the past, shared environmental influences on personality traits have been found to be negligible in behavior genetic studies (e.g., Bouchard & McGue, 2003). However, most studies have been based on biometrical modeling of twins only. Failure to meet key assumptions of the classical twin design could lead to biased estimates of shared environmental effects. Alternative approaches to the etiology of personality are needed. In the current study we estimated the impact of shared environmental factors on adolescent personality by simultaneously modeling both twin and adoption data. We found evidence for significant shared environmental influences on Multidimensional Personality Questionnaire (MPQ) Absorption (15% variance explained), Alienation (10%), Harm Avoidance (14%), and Traditionalism (26%) scales. Additionally, we found that in most cases biometrical models constraining parameter estimates to be equal across study type (twins versus adoptees) fit no worse than models allowing these parameters to vary; this suggests that results converge across study design despite the potential (sometimes opposite) biases of twin and adoption studies. Thus, we can be more confident that our findings represent the true contribution of shared environmental variance to personality development. PMID:24065564

Smoking and long-term labour market outcomes.

PubMed

Böckerman, Petri; Hyytinen, Ari; Kaprio, Jaakko

2015-07-01

To examine the long-term effects of smoking on labour market outcomes using twin data matched to register-based individual information on earnings. Twin data for Finnish men born 1945-1957 was used to remove the shared environmental and genetic factors. The results were subjected to extensive robustness testing. Lifetime cigarette consumption was measured by (cumulative) cigarette pack-years in early adulthood. The average of an individual's earnings (and, alternatively, taxable income) was measured over a subsequent 15-year period in later adulthood. Smokers have lower long-term income and earnings. For example, controlling for the shared environmental and genetic factors using the data on genetically identical twins, smoking is negatively associated with lifetime income (p=0.015). The negative association was also robust to the use of various covariates, such as education, health indicators and extraversion. Smoking is negatively related to long-term labour market outcomes. The provision of information about the indirect monetary costs of smoking may thus complement the policy efforts that aim at educating consumers about the health costs of smoking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Offering to Share: How to Put Heads Together in Autism Neuroimaging

ERIC Educational Resources Information Center

Belmonte, Matthew K.; Mazziotta, John C.; Minshew, Nancy J.; Evans, Alan C.; Courchesne, Eric; Dager, Stephen R.; Bookheimer, Susan Y.; Aylward, Elizabeth H.; Amaral, David G.; Cantor, Rita M.; Chugani, Diane C.; Dale, Anders M.; Davatzikos, Christos; Gerig, Guido; Herbert, Martha R.; Lainhart, Janet E.; Murphy, Declan G.; Piven, Joseph; Reiss, Allan L.; Schultz, Robert T.; Zeffiro, Thomas A.; Levi-Pearl, Susan; Lajonchere, Clara; Colamarino, Sophia A.

2008-01-01

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including…

Understanding the covariation of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms: A population-based adult twin study.

PubMed

Pinto, Rebecca; Monzani, Benedetta; Leckman, James F; Rück, Christian; Serlachius, Eva; Lichtenstein, Paul; Mataix-Cols, David

2016-10-01

Chronic tic disorders (TD), attention-deficit/hyperactivity-disorder (ADHD), and obsessive-compulsive disorder (OCD) frequently co-occur in clinical and epidemiological samples. Family studies have found evidence of shared familial transmission between TD and OCD, whereas the familial association between these disorders and ADHD is less clear. This study aimed to investigate to what extent liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms is caused by shared or distinct genetic or environmental influences, in a large population-representative sample of Swedish adult twins (n = 21,911). Tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms showed modest, but significant covariation. Model fitting suggested a latent liability factor underlying the three phenotypes. This common factor was relatively heritable, and explained significantly less of the variance of attention-deficit/hyperactivity symptom liability. The majority of genetic variance was specific rather than shared. The greatest proportion of total variance in liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms was attributed to specific non-shared environmental influences. Our findings suggest that the co-occurrence of tics and obsessive-compulsive symptoms, and to a lesser extent attention-deficit/hyperactivity symptoms, can be partly explained by shared etiological influences. However, these phenotypes do not appear to be alternative expressions of the same underlying genetic liability. Further research examining sub-dimensions of these phenotypes may serve to further clarify the association between these disorders and identify more genetically homogenous symptom subtypes. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Democratization of genetic data: connecting government approval of clinical tests with data sharing

PubMed Central

Ross, Theodora S.

2015-01-01

Abstract When a doctor orders a genetic test, patients assume that the test will yield a useful result to guide how their physicians take care of them. That assumption is frequently correct, but not always. Until recently, a genetic test only interrogated the sequence of one or two genes. Now, DNA-sequencing technologies are so fast and cheap that they have enabled clinicians to sequence panels of genes that may or may not be relevant to the patient's condition. The technology has outpaced our ability to interpret the results. Connecting approval of clinical tests to data sharing could help close this gap. PMID:27148568

Genetically determined schizophrenia is not associated with impaired glucose homeostasis.

PubMed

Polimanti, Renato; Gelernter, Joel; Stein, Dan J

2018-05-01

Here, we used data from large genome-wide association studies to test the presence of causal relationships, conducting a Mendelian randomization analysis; and shared molecular mechanisms, calculating the genetic correlation, among schizophrenia, type 2 diabetes (T2D), and impaired glucose homeostasis. Although our Mendelian randomization analysis was well-powered, no causal relationship was observed between schizophrenia and T2D, or traits related to glucose impaired homeostasis. Similarly, we did not observe any global genetic overlap among these traits. These findings indicate that there is no causal relationships or shared mechanisms between schizophrenia and impaired glucose homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Democratization of genetic data: connecting government approval of clinical tests with data sharing.

PubMed

Ross, Theodora S

2015-10-01

When a doctor orders a genetic test, patients assume that the test will yield a useful result to guide how their physicians take care of them. That assumption is frequently correct, but not always. Until recently, a genetic test only interrogated the sequence of one or two genes. Now, DNA-sequencing technologies are so fast and cheap that they have enabled clinicians to sequence panels of genes that may or may not be relevant to the patient's condition. The technology has outpaced our ability to interpret the results. Connecting approval of clinical tests to data sharing could help close this gap.

Similar genetic architecture with shared and unique quantitative trait loci for bacterial cold water disease resistance in two rainbow trout breeding populations

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57K SNP array and a genome phys...

Predicting individual differences in reading comprehension: a twin study

PubMed Central

Cutting, Laurie; Deater-Deckard, Kirby; DeThorne, Laura S.; Justice, Laura M.; Schatschneider, Chris; Thompson, Lee A.; Petrill, Stephen A.

2010-01-01

We examined the Simple View of reading from a behavioral genetic perspective. Two aspects of word decoding (phonological decoding and word recognition), two aspects of oral language skill (listening comprehension and vocabulary), and reading comprehension were assessed in a twin sample at age 9. Using latent factor models, we found that overlap among phonological decoding, word recognition, listening comprehension, vocabulary, and reading comprehension was primarily due to genetic influences. Shared environmental influences accounted for associations among word recognition, listening comprehension, vocabulary, and reading comprehension. Independent of phonological decoding and word recognition, there was a separate genetic link between listening comprehension, vocabulary, and reading comprehension and a specific shared environmental link between vocabulary and reading comprehension. There were no residual genetic or environmental influences on reading comprehension. The findings provide evidence for a genetic basis to the “Simple View” of reading. PMID:20814768

Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits.

PubMed

Wu, Yang; Zeng, Jian; Zhang, Futao; Zhu, Zhihong; Qi, Ting; Zheng, Zhili; Lloyd-Jones, Luke R; Marioni, Riccardo E; Martin, Nicholas G; Montgomery, Grant W; Deary, Ian J; Wray, Naomi R; Visscher, Peter M; McRae, Allan F; Yang, Jian

2018-03-02

The identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i.e., pleiotropy). We identify pleiotropic associations between 7858 DNAm sites and 2733 genes. These DNAm sites are enriched in enhancers and promoters, and >40% of them are mapped to distal genes. Further pleiotropic association analyses, which link both the methylome and transcriptome to 12 complex traits, identify 149 DNAm sites and 66 genes, indicating a plausible mechanism whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription through DNAm.

Genetic overlap between polycystic ovary syndrome and bipolar disorder: the endophenotype hypothesis.

PubMed

Jiang, Bowen; Kenna, Heather A; Rasgon, Natalie L

2009-12-01

Polycystic Ovary Syndrome (PCOS) is a polygenic disorder caused by the interaction of susceptible genomic polymorphisms with environmental factors. PCOS, characterized by hyperandrogenism and menstrual abnormalities, has a higher prevalence in women with Bipolar Disorder (BD). Theories explaining this high prevalence have included the effect of PCOS itself or the effect of drugs such as Valproate, which may cause PCOS either directly or indirectly. Incidentally, metabolic abnormalities are observed in both bipolar and PCOS patients. Endophenotypes such as insulin resistance, obesity, and hyperglycemia are common among BD and PCOS patients, suggesting some degree of pathophysiological overlap. Since both BD and PCOS are complex polygenetic diseases, the endophenotype overlap may be the result of common genetic markers. This paper postulates that shared clinical endophenotypes between PCOS and BD indicate common pathophysiological platforms and will review these for the potential of genetic overlap between the two disorders.

Biotech Information-Sharing Memorandum of Understanding

EPA Pesticide Factsheets

EPA, FDA, and the U.S. Department of Agriculture's Animal and Plant Health Inspection Service/Biotechnology Regulatory Services share the regulatory oversight over genetically engineered plants and the foods derived from such plants.

Is Mania the Hypertension of the Mood? Discussion of A Hypothesis

PubMed Central

Rihmer, Zoltán; Gonda, Xénia; Döme, Péter

2017-01-01

Abstract: Beyond both being biphasic/bidirectional disorders (hypo)mania and essential hypertension share a surprising number of similarities and an overlap between their genetics, biological background, underlying personality and temperamental factors, precipitating factors, comorbidity and response to treatment, indicating a possibly partially shared biological background. Based on theoretical knowledge, similarities related to characteristics, manifestation and course, and the results of pharmacological studies related to the effects and side effects of pharmacotherapies used in the treatment of these two distinct disorders, the authors outline a hypothesis discussing the similar origins of these two phenomena and thus mania being the hypertension of mood in memory of Athanasios Koukopoulos, one of the greatest researchers and theoreticists of mania of all time. PMID:28503115

Genetic and Environmental Influences on Frontal EEG Asymmetry and Alpha Power in 9–10 Year Old Twins

PubMed Central

Gao, Yu; Tuvblad, Catherine; Raine, Adrian; Lozano, Dora I.; Baker, Laura A.

2008-01-01

Modest genetic influences on frontal EEG asymmetry have been found in adults, but little is known about its genetic origins in children. Resting frontal asymmetry and alpha power were examined in 951 9–10-year-old twins. Results showed that in both males and females: (1) a modest but significant amount of variance in frontal asymmetry was accounted for by genetic factors (11–27%) with the remainder accounted for by non-shared environmental influences, and (2) alpha power were highly heritable, with 70–85% of the variance accounted for by genetic factors. Results suggest that the genetic architecture of frontal asymmetry and alpha power in late childhood are similar to that in adulthood and that the high non-shared environmental influences on frontal asymmetry may reflect environmentally-influenced individual differences in the maturation of frontal cortex as well as state-dependent influences on specific measurements. PMID:19386046

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

PubMed

Eppinga, Ruben N; Hagemeijer, Yanick; Burgess, Stephen; Hinds, David A; Stefansson, Kari; Gudbjartsson, Daniel F; van Veldhuisen, Dirk J; Munroe, Patricia B; Verweij, Niek; van der Harst, Pim

2016-12-01

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10 -8 ); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10 -7 ) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.

An overview of human genetic privacy.

PubMed

Shi, Xinghua; Wu, Xintao

2017-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. © 2016 New York Academy of Sciences.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

PubMed

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

PubMed Central

Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

Genetic and Environmental Influences on Global Family Conflict

PubMed Central

Horwitz, Briana N.; Neiderhiser, Jenae M.; Ganiban, Jody M.; Spotts, Erica L.; Lichtenstein, Paul; Reiss, David

2010-01-01

This study examined genetic and environmental influences on global family conflict. The sample comprised 872 same-sex pairs of twin parents, their spouses/partners and one adolescent child per twin from the Twin and Offspring Study in Sweden (TOSS). The twins, spouses and child each reported on the degree of family conflict, and there was significant agreement among the family members’ ratings. These shared perspectives were explained by one common factor, indexing global family conflict. Genetic influences explained 36% of the variance in this common factor, suggesting that twins’ heritable characteristics contribute to family conflict, via genotype-environment correlation. Nonshared environmental effects explained the remaining 64% of this variance, indicating that twins’ unique childhood and/or current family experiences also play an important role. PMID:20438198

Attention Deficit Hyperactivity Disorder with Reading Disabilities: Preliminary Genetic Findings on the Involvement of the ADRA2A Gene

ERIC Educational Resources Information Center

Stevenson, J.; Langley, K.; Pay, H.; Payton, A.; Worthington, J.; Ollier, W.; Thapar, A.

2005-01-01

Background: Attention deficit/hyperactivity disorder (ADHD) and reading disability (RD) tend to co-occur and quantitative genetic studies have shown this to arise primarily through shared genetic influences. However, molecular genetic studies have shown different genes to be associated with each of these conditions. Neurobiological studies have…

GENETIC AND ENVIRONMENTAL EFFECTS ON BODY MASS INDEX DURING ADOLESCENCE: A PROSPECTIVE STUDY AMONG FINNISH TWINS

PubMed Central

Lajunen, Hanna-Reetta; Kaprio, Jaakko; Keski-Rahkonen, Anna; Rose, Richard J.; Pulkkinen, Lea; Rissanen, Aila; Silventoinen, Karri

2009-01-01

Objective To study genetic and environmental factors affecting body mass index (BMI) and BMI phenotypic correlations across adolescence. Design Prospective, population-based, twin cohort study. Subjects and methods We used twin modeling in 2413 monozygotic and same-sex and opposite-sex dizygotic Finnish twin pairs born in 1983–1987 and assessed by self-report questionnaires at 11–12, 14, and 17 years. Results Heritability of BMI was estimated to be 0.58–0.69 among 11–12- and 14-year-old boys and girls, 0.83 among 17-year-old boys and 0.74 among girls. Common environmental effects shared by siblings were 0.15–0.24 among 11–12- and 14-year-old boys and girls but no longer discernible at 17 y. Unique environmental effects were 0.15–0.23. Additive genetic factors explained 90–96% of the BMI phenotypic correlations across adolescence, whereas unique environmental factors explained the rest. Common environment had no effect on BMI phenotypic correlations. Conclusions The genetic contribution to BMI is strong during adolescence, and it mainly explains BMI phenotypic correlations across adolescence. Common environmental factors have an effect on BMI during early adolescence, but that effect disappears by late adolescence. PMID:19337205

DEPRESSION AND INTERNALLY DIRECTED AGGRESSION: GENETIC AND ENVIRONMENTAL CONTRIBUTIONS

PubMed Central

Haddad, Suzanne K.; Neiderhiser, Jenae M.; Spotts, Erica L.; Ganiban, Jody; Lichtenstein, Paul; Reiss, David

2013-01-01

This study uses behavior genetic (BG) methodology to investigate Freud’s theory of depression as aggression directed toward the self (1930) and the extent to which genetically and environmentally influenced aggressive tendencies contribute to depressive symptoms. Data from the Twin and Offspring Study in Sweden (TOSS) is used to demonstrate how, in estimating shared and unique environmental influences, BG methods can inform psychoanalytic theory and practice, particularly because of their shared emphasis on the importance of individual experience in development. The TOSS sample consists of 909 pairs of adult twins, their partners, and one adolescent child per couple. The Center for Epidemiologic Studies Depression Scale (Radloff 1977) was used to measure depressive symptoms and the Karolinska Scales of Personality (Schalling and Edman 1993) to measure internally directed aggression. Genetic analyses indicated that for both men and women, their unique experiences as well as genetic factors contributed equally to the association between internally directed aggression and depressive symptoms. These findings support Freud’s theory that constitutionally based differences in aggression, along with individual experiences, contribute to a person’s depressive symptoms. Establishing that an individual’s unique, not shared, experiences and perceptions contribute to depressive symptoms and internally directed aggression reinforces the use of patient-specific treatment approaches implemented in psychoanalytic psychotherapy or psychoanalysis. PMID:18515705

The impact of genetics on future drug discovery in schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

2017-07-01

Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

Rodriguez and Pennington Address Proteogenomics and Data Sharing in the Journal Cell | Office of Cancer Clinical Proteomics Research

Cancer.gov

Precision medicine is an approach that allows doctors to understand how a patient's genetic profile may cause cancer to grow and spread, leading to a more personalized treatment strategy based on molecular characterization of a person's tumor. However, precision medicine as a genomics-based approach does not yet apply to all patients because genetic mutations do not always lead to changes of the corresponding proteins. Therefore, integrating genomics and proteomics data, or proteogenomics, presents as a new approach that may help make precision medicine a more effective treatment option for patients.

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

PubMed

Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

2016-01-01

Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific environmental factors unshared with OCS and HD.

Cross-generational transmission from drug abuse in parents to attention-deficit/hyperactivity disorder in children

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2016-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) predisposes to drug abuse (DA) and twin studies suggest shared genetic effects. We here seek to determine, using adoption and adoption-like samples, the magnitude of the cross-generational transmission from DA in parents to ADHD in their children and clarify the degree to which this arises from genetic v. rearing effects. Method We ascertained ADHD and DA from multiple Swedish registries. Statistical analysis was performed by Cox and path models. Results Risk for ADHD was significantly and similarly increased in the offspring of biological mothers and fathers with DA who did v. did not rear their offspring. Risk for ADHD was not elevated in the offspring of adoptive or step-parents with DA. Conclusions Cross-generational transmission was observed from DA in parents to ADHD in their children. An analysis of adoptive and adoptive-like parent–offspring relationships suggested that this transmission results from genetic and not from rearing effects. PMID:26928631

Differential Antidepressant-Like Response to Lithium Treatment between Mouse Strains: Effects of Sex, Maternal Care, and Mixed Genetic Background

PubMed Central

Can, Adem; Piantadosi, Sean C.; Gould, Todd D.

2013-01-01

Background Lithium is a mood stabilizer with both antidepressant and antimanic properties, though its mechanism of action is unclear. Identifying the genetic factors that influence lithium's therapeutic actions will be an important step to assist in identifying such mechanisms. We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain. Objectives To assess the roles of both genetic, and non-genetic factors such as sex and non-shared environmental factors that may mediate differential behavioral responses to lithium. Methods Mice were treated with lithium for ten days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal. We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains. Results Neither sex nor maternal care significantly influenced the differential antidepressant-like profile of lithium. Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain, but had no effects in BALB/cJ mice. Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain. Conclusions Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains. Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium's therapeutic actions. PMID:23503701

Improving production efficiency through genetic selection

USDA-ARS?s Scientific Manuscript database

The goal of dairy cattle breeding is to increase productivity and efficiency by means of genetic selection. This is possible because related animals share some of their DNA in common, and we can use statistical models to predict the genetic merit animals based on the performance of their relatives. ...

Do Knowledge Arrangements Affect Student Reading Comprehension of Genetics?

ERIC Educational Resources Information Center

Wu, Jen-Yi; Tung, Yu-Neng; Hwang, Bi-Chi; Lin, Chen-Yung; Che-Di, Lee; Chang, Yung-Ta

2014-01-01

Various sequences for teaching genetics have been proposed. Three seventh-grade biology textbooks in Taiwan share similar key knowledge assemblages but have different knowledge arrangements. To investigate the influence of knowledge arrangements on student understanding of genetics, we compared students' reading comprehension of the three texts…

Maximum-likelihood estimation of recent shared ancestry (ERSA).

PubMed

Huff, Chad D; Witherspoon, David J; Simonson, Tatum S; Xing, Jinchuan; Watkins, W Scott; Zhang, Yuhua; Tuohy, Therese M; Neklason, Deborah W; Burt, Randall W; Guthery, Stephen L; Woodward, Scott R; Jorde, Lynn B

2011-05-01

Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package.

Genetics Home Reference: lymphangioleiomyomatosis

MedlinePlus

... Genetics Share: Email Facebook Twitter Home Health Conditions LAM Lymphangioleiomyomatosis Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Lymphangioleiomyomatosis ( LAM ) is a condition that affects the lungs , the ...

The genetic architecture of liver enzyme levels: GGT, ALT and AST.

PubMed

van Beek, Jenny H D A; de Moor, Marleen H M; de Geus, Eco J C; Lubke, Gitta H; Vink, Jacqueline M; Willemsen, Gonneke; Boomsma, Dorret I

2013-07-01

High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

International Policies on Sharing Genomic Research Results with Relatives: Approaches to Balancing Privacy with Access

PubMed Central

Branum, Rebecca; Wolf, Susan M.

2015-01-01

Returning genetic research results to raises complex issues. In order to inform the U.S. debate, this paper analyzes international law and policies governing the sharing of genetic research results with relatives and identifies key themes and lessons. The laws and policies from other countries demonstrate a range of approaches to balancing individual privacy and autonomy with family access for health benefit, offering important lessons for further development of approaches in the United States. PMID:26479568

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus.

PubMed

Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Blanco, Francisco J; Suarez, Ana; Santos, Maria Jose; Papasteriades, Chryssa; Carreira, Patricia; Pullmann, Rudolf; Ordi-Ros, Josep; Marchini, Maurizio; Skopouli, Fotini N; Bijl, Marc; Barrizone, Nadia; Sebastiani, Gian Domenico; Migliaresi, Sergio; Witte, Torsten; Lauwerys, Bernard R; Kovacs, Attila; Ruzickova, Sarka; Gomez-Reino, Juan J; Gonzalez, Antonio

2014-06-19

We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

PubMed Central

2014-01-01

Introduction We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Methods Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRSs). Results Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRSs. GRSs were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10−16) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10−7), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Conclusion Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women. PMID:24946689

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition

PubMed Central

Hubbard, Leon; Tansey, Katherine E.; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D.; Moran, Jennifer L.; McCarroll, Steven A.; Linden, David E. J.; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.; Zammit, Stanley

2016-01-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophrenia en masse contribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n = 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n = 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P = .001) and lower full IQ (P = .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P = 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (r G = −.379, P = 6.62E-05) and full IQ (r G = −.202, P = 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. PMID:26678674

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.

PubMed

Hubbard, Leon; Tansey, Katherine E; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D; Moran, Jennifer L; McCarroll, Steven A; Linden, David E J; Owen, Michael J; O'Donovan, Michael C; Walters, James T R; Zammit, Stanley

2016-05-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Understanding the Relation between Anorexia Nervosa and Bulimia Nervosa in a Swedish National Twin Sample

PubMed Central

Bulik, Cynthia M; Thornton, Laura; Root, Tammy L.; Pisetsky, Emily M.; Lichtenstein, Paul; Pedersen, Nancy L.

2010-01-01

Background We present a bivariate twin analysis of anorexia nervosa (AN) and bulimia nervosa (BN) to determine the extent to which shared genetic and environmental factors contribute to liability to these disorders. Method Focusing on females from the Swedish Twin study of Adults: Genes and Environment (STAGE) (N=7000), we calculated heritability estimates for narrow and broad AN and BN and estimated their genetic correlation. Results In the full model, the heritability estimate for narrow AN was (a2 = .57; 95% CI: .00, .81) and for narrow BN (a2 = .62; 95% CI: .08, .70) with the remaining variance accounted for by unique environmental factors. Shared environmental factors estimates were (c2 = .00; 95% CI: .00, .67) for AN and (c2 = .00; 95% CI: .00, .40) for BN. Moderate additive genetic (.46) and unique environmental (.42) correlations between AN and BN were observed. Heritability estimates for broad AN were lower (a2 = .29; 95% CI: .04, .43) than for narrow AN, but estimates for broad BN were similar to narrow BN. The genetic correlation for broad AN and BN was .79 and the unique environmental correlation was .44. Conclusions We highlight the contribution of additive genetic factors to both narrow and broad AN and BN and demonstrate a moderate overlap of both genetic and unique environmental factors that influence the two conditions. Common concurrent and sequential comorbidity of AN and BN can in part be accounted for by shared genetic and environmental influences on liability although independent factors also operative. PMID:19828139

Genes for Reading and Spelling

ERIC Educational Resources Information Center

Bates, Timothy C.

2006-01-01

This article reviews research on the behavioral and molecular genetics of reading and, where available, spelling. Recent research is summarized, suggesting that reading and spelling appear to share a common genetic basis, and that dyslexia lies on a genetic continuum with normal variance in reading skill. Research also suggests that while many of…

Environmental Influences on Reading-Related Outcomes: An Adoption Study

ERIC Educational Resources Information Center

Petrill, Stephen A.; Deater-Deckard, Kirby; Schatschneider, Christopher; Davis, Chayna

2007-01-01

Evidence from intervention studies, quantitative genetic and molecular genetic studies suggests that genetic, and to a lesser extent, shared environmental influences are important to the development of reading and related cognitive skills. The Northeast-Northwest Collaborative Adoption Projects (N2CAP) is a sample of 241 adoptive families,…

Genetic and Environmental Influences on Vocabulary and Reading Development

ERIC Educational Resources Information Center

Olson, Richard K.; Keenan, Janice M.; Byrne, Brian; Samuelsson, Stefan; Coventry, William L.; Corley, Robin; Wadsworth, Sally J.; Willcutt, Erik G.; DeFries, John C.; Pennington, Bruce F.; Hulslander, Jacqueline

2011-01-01

Genetic and environmental relations between vocabulary and reading skills were explored longitudinally from preschool through Grades 2 and 4. At preschool there were strong shared-environment and weak genetic influences on both vocabulary and print knowledge but substantial differences in their source. Separation of etiology for vocabulary and…

Revisiting the Effect of Marital Support on Depressive Symptoms in Mothers and Fathers: A Genetically Informed Study

PubMed Central

Beam, Christopher R.; Horn, Erin E.; Hunt, Stacy Karagis; Emery, Robert E.; Turkheimer, Eric; Martin, Nick

2011-01-01

This article uses a genetically informed design to evaluate whether (1) the well-documented association between marital support and depressive symptoms is accounted for by genetic and/or shared environmental selection, (2) gender differences are found after controlling for selection effects, and (3) parenthood moderates any nonshared environmental relation between depressive symptoms and marital support. We used a sample of 1,566 pairs of same-sexed, married twins from the Australian Twin Registry to evaluate our hypotheses that (1) the predicted effect of marital support on depressive symptoms is not fully an artifact of selection, (2) the etiological sources accounting for this effect differ between husbands and wives, and (3) parenthood status moderates the effect of marital support on depressive symptoms adjusting for selection effects. The results support the first hypotheses. However, after controlling for selection, the effect of marital support on depressive symptoms was not significantly different for husbands and wives. Parenthood moderated the effect of marital support, such that after controlling for selection, marital support is more strongly associated with depressive symptoms for full-time parents than nonfull-time parents. PMID:21553961

A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Maes, Hermine H; Sundquist, Kristina; Lichtenstein, Paul; Sundquist, Jan

2015-04-01

Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male-male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18-20% of the variance in liability, were non-specific. In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The KinFact intervention - a randomized controlled trial to increase family communication about cancer history.

PubMed

Bodurtha, Joann N; McClish, Donna; Gyure, Maria; Corona, Rosalie; Krist, Alexander H; Rodríguez, Vivian M; Maibauer, Alisa M; Borzelleca, Joseph; Bowen, Deborah J; Quillin, John M

2014-10-01

Knowing family history is important for understanding cancer risk, yet communication within families is suboptimal. Providing strategies to enhance communication may be useful. Four hundred ninety women were recruited from urban, safety-net, hospital-based primary care women's health clinics. Participants were randomized to receive the KinFact intervention or the control handout on lowering risks for breast/colon cancer and screening recommendations. Cancer family history was reviewed with all participants. The 20-minute KinFact intervention, based in communication and behavior theory, included reviewing individualized breast/colon cancer risks and an interactive presentation about cancer and communication. Study outcomes included whether participants reported collecting family history, shared cancer risk information with relatives, and the frequency of communication with relatives. Data were collected at baseline, 1, 6, and 14 months. Overall, intervention participants were significantly more likely to gather family cancer information at follow-up (odds ratio [OR]: 2.73; 95% confidence interval [CI]: 2.01, 3.71) and to share familial cancer information with relatives (OR: 1.85; 95% CI: 1.37, 2.48). Communication frequency (1=not at all; 4=a lot) was significantly increased at follow-up (1.67 vs. 1.54). Differences were not modified by age, race, education, or family history. However, effects were modified by pregnancy status and genetic literacy. Intervention effects for information gathering and frequency were observed for nonpregnant women but not for pregnant women. Additionally, intervention effects were observed for information gathering in women with high genetic literacy, but not in women with low genetic literacy. The KinFact intervention successfully promoted family communication about cancer risk. Educating women to enhance their communication skills surrounding family history may allow them to partner more effectively with their families and ultimately their providers in discussing risks and prevention.

Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar.

PubMed

Harrison, Steven M; Dolinsky, Jill S; Knight Johnson, Amy E; Pesaran, Tina; Azzariti, Danielle R; Bale, Sherri; Chao, Elizabeth C; Das, Soma; Vincent, Lisa; Rehm, Heidi L

2017-10-01

Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar-thereby allowing identification of differences and motivation to resolve those differences-is critical to moving toward more consistent variant interpretations.Genet Med advance online publication 09 March 2017.

A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

PubMed

Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

2015-08-01

In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. © 2015 Stichting International Foundation for Animal Genetics.

Genetics Home Reference: keratoconus

MedlinePlus

... Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Home Health Conditions Keratoconus Keratoconus Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Keratoconus ...

Smoking and caffeine consumption: a genetic analysis of their association.

PubMed

Treur, Jorien L; Taylor, Amy E; Ware, Jennifer J; Nivard, Michel G; Neale, Michael C; McMahon, George; Hottenga, Jouke-Jan; Baselmans, Bart M L; Boomsma, Dorret I; Munafò, Marcus R; Vink, Jacqueline M

2017-07-01

Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. © 2016 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Smoking and caffeine consumption: a genetic analysis of their association

PubMed Central

Taylor, Amy E.; Ware, Jennifer J.; Nivard, Michel G.; Neale, Michael C.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

2016-01-01

Abstract Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta‐analyses of genome‐wide association studies on smoking and caffeine, the genetic correlation was calculated by LD‐score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD‐score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. PMID:27027469

Unstructured Socializing with Peers and Delinquent Behavior: A Genetically Informed Analysis.

PubMed

Meldrum, Ryan C; Barnes, J C

2017-09-01

A large body of research finds that unstructured socializing with peers is positively associated with delinquency during adolescence. Yet, existing research has not ruled out the potential for confounding due to genetic factors and factors that can be traced to environments shared between siblings. To fill this void, the current study examines whether the association between unstructured socializing with peers and delinquent behavior remains when accounting for genetic factors, shared environmental influences, and a variety of non-shared environmental covariates. We do so by using data from the twin subsample of the National Longitudinal Study of Adolescent to Adult Health (n = 1200 at wave 1 and 1103 at wave 2; 51% male; mean age at wave 1 = 15.63). Results from both cross-sectional and lagged models indicate the association between unstructured socializing with peers and delinquent behavior remains when controlling for both genetic and environmental influences. Supplementary analyses examining the association under different specifications offer additional, albeit qualified, evidence supportive of this finding. The study concludes with a discussion highlighting the importance of limiting free time with friends in the absence of authority figures as a strategy for reducing delinquency during adolescence.

Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

PubMed

Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

2010-01-01

Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

The US Culture Collection Network responding to the requirements of the Nagoya Protocol on Access and Benefit Sharing

USDA-ARS?s Scientific Manuscript database

The US Culture Collection Network held a meeting to share information about how collections are responding to the requirements of the recently enacted Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Bio...

Chronic Fatigue and Personality: A Twin Study of Causal Pathways and Shared Liabilities

PubMed Central

Poeschla, Brian; Strachan, Eric; Dansie, Elizabeth; Buchwald, Dedra S.; Afari, Niloofar

2013-01-01

Background The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue. Purpose To examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample. Methods We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO-FFI. Using a co-twin control design, we examined the association between personality and chronic fatigue. Results Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors. Conclusions Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bi-directional. PMID:23361410

Association between stressful life events and psychotic experiences in adolescence: evidence for gene-environment correlations.

PubMed

Shakoor, Sania; Zavos, Helena M S; Haworth, Claire M A; McGuire, Phillip; Cardno, Alastair G; Freeman, Daniel; Ronald, Angelica

2016-06-01

Stressful life events (SLEs) are associated with psychotic experiences. SLEs might act as an environmental risk factor, but may also share a genetic propensity with psychotic experiences. To estimate the extent to which genetic and environmental factors influence the relationship between SLEs and psychotic experiences. Self- and parent reports from a community-based twin sample (4830 16-year-old pairs) were analysed using structural equation model fitting. SLEs correlated with positive psychotic experiences (r = 0.12-0.14, all P<0.001). Modest heritability was shown for psychotic experiences (25-57%) and dependent SLEs (32%). Genetic influences explained the majority of the modest covariation between dependent SLEs and paranoia and cognitive disorganisation (bivariate heritabilities 74-86%). The relationship between SLEs and hallucinations and grandiosity was explained by both genetic and common environmental effects. Further to dependent SLEs being an environmental risk factor, individuals may have an underlying genetic propensity increasing their risk of dependent SLEs and positive psychotic experiences. © The Royal College of Psychiatrists 2016.

Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts.

PubMed

Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Hjelmborg, Jacob V B; Möller, Sören; Honda, Chika; Magnusson, Patrik K E; Pedersen, Nancy L; Ooki, Syuichi; Aaltonen, Sari; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Freitas, Duarte L; Maia, José Antonio; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J; Jang, Kerry L; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S Alexandra; Klump, Kelly L; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A; Bartels, Meike; van Beijsterveldt, Toos C E M; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Swan, Gary E; Krasnow, Ruth; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K Paige; Tucker-Drob, Elliot M; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A; Tuvblad, Catherine; Duncan, Glen E; Buchwald, Dedra; Willemsen, Gonneke; Skytthe, Axel; Kyvik, Kirsten O; Christensen, Kaare; Öncel, Sevgi Y; Aliev, Fazil; Rasmussen, Finn; Goldberg, Jack H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

2016-06-23

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

Accounting for the Physical and Mental Health Benefits of Entry Into Marriage: A Genetically Informed Study of Selection and Causation

PubMed Central

Horn, Erin E.; Xu, Yishan; Beam, Christopher R.; Turkheimer, Eric; Emery, Robert E.

2013-01-01

Married adults show better psychological adjustment and physical health than their separated/divorced or never-married counterparts. However, this apparent “marriage benefit” may be due to social selection, social causation, or both processes. Genetically informed research designs offer critical advantages for helping to disentangle selection from causation by controlling for measured and unmeasured genetic and shared environmental selection. Using young-adult twin and sibling pairs from the National Longitudinal Study of Adolescent Health (Harris, 2009), we conducted genetically informed analyses of the association between entry into marriage, cohabitation, or singlehood and multiple indices of psychological and physical health. The relation between physical health and marriage was completely explained by nonrandom selection. For internalizing behaviors, selection did not fully explain the benefits of marriage or cohabitation relative to being single, whereas for externalizing symptoms, marriage predicted benefits over cohabitation. The genetically informed approach provides perhaps the strongest nonexperimental evidence that these observed effects are causal. PMID:23088795

Exploring How Symptoms of Attention-Deficit/Hyperactivity Disorder Are Related to Reading and Mathematics Performance: General Genes, General Environments

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Willcutt, Erik; Thompson, Lee A.; Schatschneider, Christopher; Deater-Deckard, Kirby; Cutting, Laurie E.

2013-01-01

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance. PMID:20966487

A behavioral genetic study of intrapersonal and interpersonal dimensions of narcissism.

PubMed

Luo, Yu L L; Cai, Huajian; Song, Hairong

2014-01-01

Narcissism, characterized by grandiose self-image and entitled feelings to others, has been increasingly prevalent in the past decades. This study examined genetic and environmental bases of two dimensions of narcissism: intrapersonal grandiosity and interpersonal entitlement. A total of 304 pairs of twins from Beijing, China completed the Narcissistic Grandiosity Scale and the Psychological Entitlement Scale. Both grandiosity (23%) and entitlement (35%) were found to be moderately heritable, while simultaneously showing considerable non-shared environmental influences. Moreover, the genetic and environmental influences on the two dimensions were mostly unique (92-93%), with few genetic and environmental effects in common (7-8%). The two dimensions of narcissism, intrapersonal grandiosity and interpersonal entitlement, are heritable and largely independent of each other in terms of their genetic and environmental sources. These findings extend our understanding of the heritability of narcissism on the one hand. On the other hand, the study demonstrates the rationale for distinguishing between intrapersonal and interpersonal dimensions of narcissism, and possibly personality in general as well.

A Behavioral Genetic Study of Intrapersonal and Interpersonal Dimensions of Narcissism

PubMed Central

Luo, Yu L. L.; Cai, Huajian; Song, Hairong

2014-01-01

Narcissism, characterized by grandiose self-image and entitled feelings to others, has been increasingly prevalent in the past decades. This study examined genetic and environmental bases of two dimensions of narcissism: intrapersonal grandiosity and interpersonal entitlement. A total of 304 pairs of twins from Beijing, China completed the Narcissistic Grandiosity Scale and the Psychological Entitlement Scale. Both grandiosity (23%) and entitlement (35%) were found to be moderately heritable, while simultaneously showing considerable non-shared environmental influences. Moreover, the genetic and environmental influences on the two dimensions were mostly unique (92–93%), with few genetic and environmental effects in common (7–8%). The two dimensions of narcissism, intrapersonal grandiosity and interpersonal entitlement, are heritable and largely independent of each other in terms of their genetic and environmental sources. These findings extend our understanding of the heritability of narcissism on the one hand. On the other hand, the study demonstrates the rationale for distinguishing between intrapersonal and interpersonal dimensions of narcissism, and possibly personality in general as well. PMID:24695616

Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

PubMed Central

Kijas, James W.; Lenstra, Johannes A.; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R.; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

2012-01-01

Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. PMID:22346734

Gene-environment correlation in the development of adolescent substance abuse: selection effects of child personality and mediation via contextual risk factors.

PubMed

Hicks, Brian M; Johnson, Wendy; Durbin, C Emily; Blonigen, Daniel M; Iacono, William G; McGue, Matt

2013-02-01

We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14 and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11 (willingness to follow rules and endorse conventional values) predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11 (social engagement and assurance, thrill seeking, and stress resilience) also predicted substance abuse directly but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse.

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

PubMed Central

2016-01-01

Background Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing. Objective To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose. Methods In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews. Results We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients. Conclusion Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose. PMID:27992547

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review.

PubMed

Bader, Loulia Akram; Elewa, Hazem

2016-01-01

Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing. To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose. In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews. We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients. Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.

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

Genetic and environmental influences on adolescent rumination and its association with depressive symptoms.

PubMed

Chen, Jie; Li, Xinying

2013-11-01

Rumination is an important cognitive vulnerability for adolescent and adult depression. However, little is known about the aetiological origins of rumination, as well as its association with depression. Adolescent rumination (self-report) and depressive symptoms (self- and parent-report) were assessed in 674 pairs of same-gender Chinese adolescent twins (11-17 years of age). Females accounted for 53.7 % of the sample. There were significant correlations between self-reported rumination and self-reported depression (r = 0.41), as well as parent-reported adolescent depression (r = 0.22). Genetic influences were significant and modest on all three measures, ranging from 24 % to 42 %. The three measures were also significantly influenced by shared environment, ranging from 20 % to 28 %, and non-shared environmental factors, ranging from 30 % to 56 %. Moreover, the genetic correlations between rumination and depression were significant (within-rater: r(g) = 0.99; cross-rater: r(g) = 0.59) and largely accounted for the phenotypic correlations (within-rater: 68 %; cross-rater: 77 %), while non-shared environmental correlations were also significant (within-rater: r(e) = 0.26; cross-rater: r(e) = 0.12) and accounted for the remainder of the phenotypic correlations (within-rater: 32 %; cross-rater: 23 %). The shared environmental correlations were non-significant. No significant gender and age differences were found in aetiological models. These findings suggest that rumination may be an endophenotype reflecting genetic risk for depression.

Identifying opportunities for collaboration and growth of genetic counseling services in the Asia Region.

PubMed

Laurino, Mercy Y; Sternen, Darci L; Thompson, Jennifer K; Leppig, Kathleen A

2017-07-01

The Genetic Counseling Pre-Conference Workshop (GCPCW) was held on September 16, 2015, in Hanoi, Vietnam. We report the GCPCW outcomes obtained from pre- and post-conference questionnaires, case-review breakout session, and an open discussion of needs for genetic counseling services in the Asia region. The GCPCW participants completed questionnaires with closed- and open-ended questions regarding the status and needs of providing genetic counseling services in Asia. Utilizing thematic content analysis, common themes shared during the case-review breakout session are summarized and survey results are tabulated. Of the 71 participants, pre- and post-conference questionnaires were returned by 57 (80%) and 44 (62%) individuals, respectively. Of the 42 participants who did not identify themselves as students in training, 36 (86%) stated they are currently providing genetic counseling services. Participants cited that the most useful information obtained during the GCPCW related to the status of genetic counseling services in the region, discovery of shared challenges, professional networking, and the need to establish genetic counseling training programs and its accreditation. The GCPCW provided a collaborative forum to address current challenges and needs of genetic counseling services in the region. Strategies were identified to foster genetic counseling training and clinical service opportunities.

Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison

2017-10-01

Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms. This review of literature examines the recent advances (from 2011) in genetic exploration of positive and negative symptoms in schizophrenia. We searched electronic databases PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature using key words schizophrenia, symptoms, positive symptoms, negative symptoms, cognition, genetics, genes, genetic predisposition, and genotype in various combinations. We identified 115 articles, which are included in the review. Evidence from these studies, most of which are genetic association studies, identifies shared and unique gene associations for the symptom domains. Genes associated with neurotransmitter systems and neuronal development/maintenance primarily constitute the shared associations. Needed are studies that examine the genetic basis of specific symptoms within the broader domains in addition to functional mechanisms. Such investigations are critical to developing precision treatment and care for individuals afflicted with schizophrenia.

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

PubMed

Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-12-07

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women's Health Initiative Study.

PubMed

Crandall, Carolyn J; Manson, JoAnn E; Hohensee, Chancellor; Horvath, Steve; Wactawski-Wende, Jean; LeBlanc, Erin S; Vitolins, Mara Z; Nassir, Rami; Sinsheimer, Janet S

2017-03-01

Vasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS. In this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMS+], and Genome-Wide Association Studies of Treatment Response in Randomized Clinical Trials [GARNET] studies, total n = 17,695) of European American, African American, and Hispanic American postmenopausal women aged 50 to 79 years at baseline in the Women's Health Initiative Study. We examined genetic variation in relation to VMS (yes/no) in each study and using trans-ethnic inverse variance fixed-effects meta-analysis. A total of 11,078,977 single-nucleotide polymorphisms (SNPs) met the quality criteria. After adjustment for covariates and population structure, three SNPs (on chromosomes 3 and 11) were associated with VMS at the genome-wide threshold of 5 × 10 in the African American SHARe GWAS, but were not associated in the other cohorts. In the meta-analysis, 14 SNPs, all located on chromosome 4 in the tachykinin receptor 3 (TACR3) locus, however, had P < 5 × 10. These SNPs' effect sizes were similar across studies/participants' ancestry (odds ratio ∼1.5). Genetic variation in TACR3 may contribute to the risk of VMS. To our knowledge, this is the first GWAS to examine SNPs associated with VMS. These results support the biological hypothesis of a role for TACR3 in VMS, which was previously hypothesized from animal and human studies. Further study of these variants may lead to new insights into the biological pathways involved in VMS, which are poorly understood.

Heritability Across the Distribution: An Application of Quantile Regression

PubMed Central

Petrill, Stephen A.; Hart, Sara A.; Schatschneider, Christopher; Thompson, Lee A.; Deater-Deckard, Kirby; DeThorne, Laura S.; Bartlett, Christopher

2016-01-01

We introduce a new method for analyzing twin data called quantile regression. Through the application presented here, quantile regression is able to assess the genetic and environmental etiology of any skill or ability, at multiple points in the distribution of that skill or ability. This method is compared to the Cherny et al. (Behav Genet 22:153–162, 1992) method in an application to four different reading-related outcomes in 304 pairs of first-grade same sex twins enrolled in the Western Reserve Reading Project. Findings across the two methods were similar; both indicated some variation across the distribution of the genetic and shared environmental influences on non-word reading. However, quantile regression provides more details about the location and size of the measured effect. Applications of the technique are discussed. PMID:21877231

Genetic and environmental influences on global family conflict.

PubMed

Horwitz, Briana N; Neiderhiser, Jenae M; Ganiban, Jody M; Spotts, Erica L; Lichtenstein, Paul; Reiss, David

2010-04-01

This study examined genetic and environmental influences on global family conflict. The sample comprised 872 same-sex pairs of twin parents, their spouses/partners, and one adolescent child per twin from the Twin and Offspring Study in Sweden. The twins, spouses, and child each reported on the degree of family conflict, and there was significant agreement among the family members' ratings. These shared perspectives were explained by one common factor, indexing global family conflict. Genetic influences explained 36% of the variance in this common factor, suggesting that twins' heritable characteristics contribute to family conflict, via genotype-environment correlation. Nonshared environmental effects explained the remaining 64% of this variance, indicating that twins' unique childhood and/or current family experiences also play an important role. 2010 APA, all rights reserved

Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

PubMed

Segal, N L; Feng, R; McGuire, S A; Allison, D B; Miller, S

2009-01-01

Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. Both non-additive genetic and common environmental contributions were significant in our model (P-values<0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8-75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8-37.5%) by a common environmental component and the remaining 10.7% by an unshared component. Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

Quantitative genetics and sex-specific selection on sexually dimorphic traits in bighorn sheep

PubMed Central

Poissant, Jocelyn; Wilson, Alastair J; Festa-Bianchet, Marco; Hogg, John T; Coltman, David W

2008-01-01

Sexual conflict at loci influencing traits shared between the sexes occurs when sex-specific selection pressures are antagonistic relative to the genetic correlation between the sexes. To assess whether there is sexual conflict over shared traits, we estimated heritability and intersexual genetic correlations for highly sexually dimorphic traits (horn volume and body mass) in a wild population of bighorn sheep (Ovis canadensis) and quantified sex-specific selection using estimates of longevity and lifetime reproductive success. Body mass and horn volume showed significant additive genetic variance in both sexes, and intersexual genetic correlations were 0.24±0.28 for horn volume and 0.63±0.30 for body mass. For horn volume, selection coefficients did not significantly differ from zero in either sex. For body weight, selection coefficients were positive in females but did not differ from zero in males. The absence of detectable sexually antagonistic selection suggests that currently there are no sexual conflicts at loci influencing horn volume and body mass. PMID:18211870

Persistent Genetic and Family-Wide Environmental Contributions to Early Number Knowledge and Later Achievement in Mathematics.

PubMed

Garon-Carrier, Gabrielle; Boivin, Michel; Kovas, Yulia; Feng, Bei; Brendgen, Mara; Vitaro, Frank; Séguin, Jean R; Tremblay, Richard E; Dionne, Ginette

2017-12-01

This study investigated the stable and transient genetic and environmental contributions to individual differences in number knowledge in the transition from preschool (age 5) to Grade 1 (age 7) and to the predictive association between early number knowledge and later math achievement (age 10-12). We conducted genetic simplex modeling across these three time points. Genetic variance was transmitted from preschool number knowledge to late-elementary math achievement; in addition, significant genetic innovation (i.e., new influence) occurred at ages 10 through 12 years. The shared and nonshared environmental contributions decreased during the transition from preschool to school entry, but shared and nonshared environment contributed to the continuity across time from preschool number knowledge to subsequent number knowledge and math achievement. There was no new environmental contribution at time points subsequent to preschool. Results are discussed in light of their practical implications for children who have difficulties with mathematics, as well as for preventive intervention.

Admixture, Population Structure, and F-Statistics.

PubMed

Peter, Benjamin M

2016-04-01

Many questions about human genetic history can be addressed by examining the patterns of shared genetic variation between sets of populations. A useful methodological framework for this purpose isF-statistics that measure shared genetic drift between sets of two, three, and four populations and can be used to test simple and complex hypotheses about admixture between populations. This article provides context from phylogenetic and population genetic theory. I review how F-statistics can be interpreted as branch lengths or paths and derive new interpretations, using coalescent theory. I further show that the admixture tests can be interpreted as testing general properties of phylogenies, allowing extension of some ideas applications to arbitrary phylogenetic trees. The new results are used to investigate the behavior of the statistics under different models of population structure and show how population substructure complicates inference. The results lead to simplified estimators in many cases, and I recommend to replace F3 with the average number of pairwise differences for estimating population divergence. Copyright © 2016 by the Genetics Society of America.

Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke

PubMed Central

Rutten-Jacobs, Loes C.A.; Thijs, Vincent; Holliday, Elizabeth G.; Levi, Chris; Bevan, Steve; Malik, Rainer; Boncoraglio, Giorgio; Sudlow, Cathie; Rothwell, Peter M.; Dichgans, Martin; Markus, Hugh S.

2016-01-01

Background and Purpose— White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis. Methods— We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging–confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups. Results— The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI

Studies on Monitoring and Tracking Genetic Resources: An Executive Summary

PubMed Central

Garrity, George M.; Thompson, Lorraine M.; Ussery, David W.; Paskin, Norman; Baker, Dwight; Desmeth, Philippe; Schindel, D.E.; Ong, P.S.

2009-01-01

The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information. PMID:21304641

Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

PubMed Central

Thapar, Anita; Harold, Gordon; Rice, Frances; Ge, XiaoJia; Boivin, Jacky; Hay, Dale; van den Bree, Marianne; Lewis, Allyson

2007-01-01

Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated. Conclusion A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects. PMID:17587444

Plastid DNA Diversity Is Higher in the Island Endemic Guadalupe Cypress than in the Continental Tecate Cypress

PubMed Central

Rosas Escobar, Patricia; Gernandt, David S.; Piñero, Daniel; Garcillán, Pedro P.

2011-01-01

Background Callitropsis guadalupensis (Guadalupe cypress) is endemic to Guadalupe Island, Mexico, where it is the dominant species of the only forest. The species has suffered declining numbers following the introduction of goats to the island over 150 years ago. Callitropsis guadalupensis is closely related to Callitropsis forbesii (Tecate cypress), distributed in small isolated populations in mainland Baja California and southern California. The objective of the present study was to compare the genetic diversity of the island endemic to the continental species. Methodology/Principal Findings We measured genetic diversity in Callitropsis guadalupensis (n = 54) from Guadalupe Island and in Callitropsis forbesii (n = 100) from five populations in mainland Baja California. The plastid DNA trnS-trnG spacer and the trnL-trnF region were chosen for characterization. Thirty-four haplotypes were observed, of which six were shared between both species. One of these haplotypes was also shared with three other species, Callitropsis lusitanica, Callitropsis montana, and Callitropsis stephensonii. Haplotype diversity (h) and nucleotide diversity (π) were significantly higher for Callitropsis guadalupensis (h = 0.698, π = 0.00071) than for Callitropsis forbesii (h = 0.337, π = 0.00024). Conclusions/Significance Callitropsis guadalupensis shows no evidence of a founder effect or of a genetic bottleneck, and can be added to a growing list of insular species with higher genetic diversity than their mainland relatives. PMID:21283771

Why do we differ in number sense? Evidence from a genetically sensitive investigation☆

PubMed Central

Tosto, M.G.; Petrill, S.A.; Halberda, J.; Trzaskowski, M.; Tikhomirova, T.N.; Bogdanova, O.Y.; Ly, R.; Wilmer, J.B.; Naiman, D.Q.; Germine, L.; Plomin, R.; Kovas, Y.

2014-01-01

Basic intellectual abilities of quantity and numerosity estimation have been detected across animal species. Such abilities are referred to as ‘number sense’. For human species, individual differences in number sense are detectable early in life, persist in later development, and relate to general intelligence. The origins of these individual differences are unknown. To address this question, we conducted the first large-scale genetically sensitive investigation of number sense, assessing numerosity discrimination abilities in 837 pairs of monozygotic and 1422 pairs of dizygotic 16-year-old twin pairs. Univariate genetic analysis of the twin data revealed that number sense is modestly heritable (32%), with individual differences being largely explained by non-shared environmental influences (68%) and no contribution from shared environmental factors. Sex-Limitation model fitting revealed no differences between males and females in the etiology of individual differences in number sense abilities. We also carried out Genome-wide Complex Trait Analysis (GCTA) that estimates the population variance explained by additive effects of DNA differences among unrelated individuals. For 1118 unrelated individuals in our sample with genotyping information on 1.7 million DNA markers, GCTA estimated zero heritability for number sense, unlike other cognitive abilities in the same twin study where the GCTA heritability estimates were about 25%. The low heritability of number sense, observed in this study, is consistent with the directional selection explanation whereby additive genetic variance for evolutionary important traits is reduced. PMID:24696527

Breast Cancer in Men: Treatments and Genetic Counseling

MedlinePlus

... Products For Consumers Home For Consumers Consumer Updates Breast Cancer in Men: Treatments and Genetic Counseling Share Tweet ... knowledge for others with this disease,” Prowell says. Breast Cancer Symptoms for Men Each year, about 2,000 ...

Genetic and Environmental Associations Between Procrastination and Internalizing/Externalizing Psychopathology.

PubMed

Gustavson, Daniel E; du Pont, Alta; Hatoum, Alexander S; Hyun Rhee, Soo; Kremen, William S; Hewitt, John K; Friedman, Naomi P

2017-09-01

Recent work on procrastination has begun to unravel the genetic and environmental correlates of this problematic behavior. However, little is known about how strongly procrastination is associated with internalizing and externalizing psychopathology, and the extent to which shared genetic/environmental factors or relevant personality constructs (e.g., fear of failure, impulsivity, and neuroticism) can inform the structure of these associations. The current study examined data from 764 young adult twins who completed questionnaires assessing procrastination and personality and structured interviews regarding psychopathology symptoms. Results indicated that procrastination was positively correlated with both internalizing and externalizing latent variables, and that these correlations were driven by shared genetic influences. Moreover, the association between procrastination and internalizing was accounted for by fear of failure and neuroticism, whereas the association between procrastination and externalizing was primarily explained by impulsivity. The role of procrastination in psychopathology is discussed using a framework that highlights common and broadband-specific variance.

A twin study of perfume-related respiratory symptoms.

PubMed

Elberling, J; Lerbaek, A; Kyvik, K O; Hjelmborg, J

2009-11-01

Respiratory symptoms from environmental perfume exposure are main complaints in patients with multiple chemical sensitivities and often coincide with asthma and or eczema. In this population-based twin study we estimate the heritability of respiratory symptoms related to perfume and if co-occurrences of the symptoms in asthma, atopic dermatitis, hand eczema or contact allergy are influenced by environmental or genetic factors common with these diseases. In total 4,128 twin individuals (82%) responded to a questionnaire. The heritability of respiratory symptoms related to perfume is 0.35, 95%CI 0.14-0.54. Significant associations (p<0.05) between perfume-related respiratory symptoms and asthma, atopic dermatitis, hand eczema or contact allergy are not attributable to shared genetic or shared environmental/familial factors, except possibly for atopic dermatitis where genetic pleiotropy with respiratory symptoms to perfume is suggested by an estimated genetic correlation of 0.39, 95%CI 0.09-0.72.

Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia

PubMed Central

Yokoyama, Jennifer S.; Karch, Celeste M.; Fan, Chun C.; Bonham, Luke W.; Kouri, Naomi; Ross, Owen A.; Rademakers, Rosa; Kim, Jungsu; Wang, Yunpeng; Höglinger, Günter U.; Muller, Ulrich; Ferrari, Raffaele; Hardy, John; Momeni, Parastoo; Sugrue, Leo P.; Hess, Christopher P.; Barkovich, A. James; Boxer, Adam L.; Seeley, William W.; Rabinovici, Gil D.; Rosen, Howard J.; Miller, Bruce L.; Schmansky, Nicholas J.; Fischl, Bruce; Hyman, Bradley T.; Dickson, Dennis W.; Schellenberg, Gerard D.; Andreassen, Ole A.; Dale, Anders M.; Desikan, Rahul S.

2017-01-01

Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p-values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p < 2.0 × 10−16). Functionally, we found that these shared risk genes were associated with protein interaction and gene co-expression networks and showed enrichment for several neurodevelopmental pathways. Our findings suggest: i) novel genetic overlap between CBD and PSP beyond the MAPT locus; ii) strong ties between CBD and FTD through the MAPT clade, and; iii) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies. PMID:28271184

Personality disorder traits, family environment, and alcohol misuse: a multivariate behavioural genetic analysis.

PubMed

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

2000-06-01

This study seeks to estimate the extent to which a common genetic and environmental basis is shared between (i) traits delineating specific aspects of antisocial personality and alcohol misuse, and (ii) childhood family environments, traits delineating broad domains of personality pathology and alcohol misuse. Postal survey data were collected from monozygotic and dizygotic twin pairs. Twin pairs were recruited from Vancouver, British Columbia and London, Ontario, Canada using newspaper advertisements, media stories and twin clubs. Data obtained from 324 monozygotic and 335 dizygotic twin pairs were used to estimate the extent to which traits delineating specific antisocial personality traits and alcohol misuse shared a common genetic and environmental aetiology. Data from 81 monozygotic and 74 dizygotic twin pairs were used to estimate the degree to which traits delineating personality pathology, childhood family environment and alcohol misuse shared a common aetiology. Current alcohol misuse and personality pathology were measured using scales contained in the self-report Dimensional Assessment of Personality Pathology. Perceptions of childhood family environment were measured using the self-report Family Environment Scale. Multivariate genetic analyses showed that a subset of traits delineating components of antisocial personality (i.e. grandiosity, attention-seeking, failure to adopt social norms, interpersonal violence and juvenile antisocial behaviours) are influenced by genetic factors in common to alcohol misuse. Genetically based perceptions of childhood family environment had little relationship with alcohol misuse. Heritable personality factors that influence the perception of childhood family environment play only a small role in the liability to alcohol misuse. Instead, liability to alcohol misuse is related to genetic factors common a specific subset of antisocial personality traits describing conduct problems, narcissistic and stimulus-seeking behaviour.

Incorporating Social Media into your Support Tool Box: Points to Consider from Genetics-Based Communities.

PubMed

Rocha, Heather Mae; Savatt, Juliann M; Riggs, Erin Rooney; Wagner, Jennifer K; Faucett, W Andrew; Martin, Christa Lese

2018-04-01

Patients with newly-described or rare genetic findings are turning to social media to find and connect with others. Blogs, Facebook groups, and Twitter have all been reported as tools for patients to connect with one another. However, the preferences for social media use and privacy among patients, their families, and these communities have not been well characterized. To explore preferences about privacy and membership guidelines, an online survey was administered to two web-based patient registries, Simons Variation in Individuals Project ( www.simonsvipconnect.org ) and GenomeConnect ( www.genomeconnect.org ). Over a three-month period, invitations were sent to 2524 individuals and 103 responses (4%) were received and analyzed. Responses indicate that Facebook is the most popular resource accessed within this sample population (99%). Participants used social media to look for information about their diagnosis or test results (83%), read posts from rare disease groups or organizations (73%), participate in conversations about their diagnosis (67%), and connect with others to find support (58%). Focusing on privacy issues in social media, respondents indicate that membership and access impact the level of comfort in sharing personal or medical information. Nearly 60% of respondents felt uncomfortable sharing photos or medical information within a public Facebook group, whereas only 12% of respondents felt uncomfortable sharing in private group targeted to families alone. Using this preliminary data concerning social media use and privacy, we developed points for genetic counselors to incorporate when discussing available support resources for patients with a new, or rare, genetic diagnosis or genetic test result. Genetic counselors are trained to provide anticipatory guidance to families adapting to new genetic information, and are well-equipped to help patients consider their preferences about using social media as a source of information and support.

Sibling Facilitation Mediates the Association Between Older and Younger Sibling Alcohol Use in Late Adolescence

PubMed Central

Samek, Diana R.; McGue, Matt; Keyes, Margaret; Iacono, William G.

2014-01-01

Previous research has shown adolescent siblings are similar in their alcohol use and that this similarity is largely due to their shared environment. Using a genetically-informed sibling sample (196 full-biological pairs, 384 genetically unrelated pairs), we confirmed that the extent to which older siblings facilitate younger siblings’ alcohol use (i.e., help them get alcohol) was one factor contributing to this shared environmental association. All analyses controlled for parent and peer influences. Findings were not moderated by sibling differences in genetic relatedness, gender, or ethnicity. Proximity in sibling age strengthened these associations, somewhat. Results were especially strong for sibling pairs where the older sibling was of legal drinking age. Implications for prevention and intervention are discussed. PMID:26640355

The Genetic and Environmental Etiologies of the Relations between Cognitive Skills and Components of Reading Ability

PubMed Central

Christopher, Micaela E.; Keenan, Janice M.; Hulslander, Jacqueline; DeFries, John C.; Miyake, Akira; Wadsworth, Sally J.; Willcutt, Erik; Pennington, Bruce; Olson, Richard K.

2016-01-01

While previous research has shown cognitive skills to be important predictors of reading ability in children, the respective roles for genetic and environmental influences on these relations is an open question. The present study explored the genetic and environmental etiologies underlying the relations between selected executive functions and cognitive abilities (working memory, inhibition, processing speed, and naming speed) with three components of reading ability (word reading, reading comprehension, and listening comprehension). Twin pairs drawn from the Colorado Front Range (n = 676; 224 monozygotic pairs; 452 dizygotic pairs) between the ages of eight and 16 (M = 11.11) were assessed on multiple measures of each cognitive and reading-related skill. Each cognitive and reading-related skill was modeled as a latent variable, and behavioral genetic analyses estimated the portions of phenotypic variance on each latent variable due to genetic, shared environmental, and nonshared environmental influences. The covariance between the cognitive skills and reading-related skills was driven primarily by genetic influences. The cognitive skills also shared large amounts of genetic variance, as did the reading-related skills. The common cognitive genetic variance was highly correlated with the common reading genetic variance, suggesting that genetic influences involved in general cognitive processing are also important for reading ability. Skill-specific genetic variance in working memory and processing speed also predicted components of reading ability. Taken together, the present study supports a genetic association between children’s cognitive ability and reading ability. PMID:26974208

The society for craniofacial genetics and developmental biology 38th annual meeting.

PubMed

Taneyhill, Lisa A; Hoover-Fong, Julie; Lozanoff, Scott; Marcucio, Ralph; Richtsmeier, Joan T; Trainor, Paul A

2016-07-01

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, post doctoral researchers, clinicians, orthodontists, scientists, and academicians who share an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

International Policies on Sharing Genomic Research Results with Relatives: Approaches to Balancing Privacy with Access.

PubMed

Branum, Rebecca; Wolf, Susan M

2015-01-01

Returning genetic research results to relatives raises complex issues. In order to inform the U.S. debate, this paper analyzes international law and policies governing the sharing of genetic research results with relatives and identifies key themes and lessons. The laws and policies from other countries demonstrate a range of approaches to balancing individual privacy and autonomy with family access for health benefit, offering important lessons for further development of approaches in the United States. © 2015 American Society of Law, Medicine & Ethics, Inc.

Genome-wide association studies reveal similar genetic architecture with shared and unique QTL for Bacterial Cold Water Disease resistance in two rainbow trout (Oncorhynchus mykiss) breeding populations

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57K SNP array and a genome phys...

Are there shared environmental influences on attention-deficit/hyperactivity disorder? Reply to Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi [corrected] (2010).

PubMed

Burt, S Alexandra

2010-05-01

A recent large-scale meta-analysis of twin and adoption studies indicated that shared environmental influences make important contributions to most forms of child and adolescent psychopathology (Burt, 2009b). The sole exception to this robust pattern of results was observed for attention-deficit/hyperactivity disorder (ADHD), which appeared to be largely genetic (and particularly nonadditive genetic) in origin, with no observable influence of the shared environment. The central thesis of Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi [corrected] (2010) is that, contrary to these findings, shared environmental influences are important for ADHD. As evidence for this thesis, Wood et al. presented a summary of prior twin studies, followed by a discussion of 4 methodological issues that may account for my findings in Burt (2009b). I argue that, although the methodological concerns raised by Wood et al. are very important, they do not undermine my earlier results (Burt, 2009b). I close with a discussion of 2 issues that may allow for some shared environmental influences on ADHD. (c) 2010 APA, all rights reserved.

Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.

PubMed

Ozdemir, Vural; Williams-Jones, Bryn; Graham, Janice E; Preskorn, Sheldon H; Gripeos, Dimitrios; Glatt, Stephen J; Friis, Robert H; Reist, Christopher; Szabo, Sandor; Lohr, James B; Someya, Toshiyuki

2007-04-01

Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

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

Quantitative genetics of circulating Hyaluronic Acid (HA) and its correlation with hand osteoarthritis and obesity-related phenotypes in a community-based sample.

PubMed

Prakash, Jai; Gabdulina, Gulzhan; Trofimov, Svetlana; Livshits, Gregory

2017-09-01

One of the potential molecular biomarkers of osteoarthritis (OA) is hyaluronic acid (HA). HA levels may be related to the severity and progression of OA. However, little is known about the contribution of major risk factors for osteoarthritis, e.g. obesity-related phenotypes and genetics to HA variation. To clarify the quantitative effect of these factors on HA. An ethnically homogeneous sample of 911 apparently healthy European-derived individuals, assessed for radiographic hand osteoarthritis (RHOA), HA, leptin, adiponectin, and several anthropometrical measures of obesity-related phenotypes was studied. Model-based quantitative genetic analysis was used to reveal genetic and shared environmental factors affecting the variation of the study's phenotypes. The HA levels significantly correlated with the age, RHOA, adiponectin, obesity-related phenotypes, and the waist-to-hip ratio. The putative genetic effects contributed significantly to the variation of HA (66.2 ± 9.3%) and they were also significant factors in the variations of all the other studied phenotypes, with the heritability estimate ranging between 0.122 ± 4.4% (WHR) and 45.7 ± 2.2% (joint space narrowing). This is the first study to report heritability estimates of HA variation and its correlation with obesity-related phenotypes, ADP and RHOA. However, the nature of genetic effects on HA and its correlation with other study phenotypes require further clarification.

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

PubMed

Liu, Jimmy Z; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Dayani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C; Alizadeh, Behrooz Z; Parkes, Miles; Bk, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

2015-09-01

Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

A twin study of spatial and non-spatial delayed response performance in middle age.

PubMed

Kremen, William S; Mai, Tuan; Panizzon, Matthew S; Franz, Carol E; Blankfeld, Howard M; Xian, Hong; Eisen, Seth A; Tsuang, Ming T; Lyons, Michael J

2011-06-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. Copyright © 2011 Elsevier Inc. All rights reserved.

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

PubMed Central

Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Dayani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C; Alizadeh, Behrooz Z; Parkes, Miles; BK, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

2016-01-01

Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here, we report the first trans-ethnic association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East-Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of IBD risk loci, the direction and magnitude of effect is consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by a combination of differences in allele frequencies (NOD2), effect sizes (TNFSF15, ATG16L1) or a combination of both (IL23R, IRGM). Our results provide biological insights into the pathogenesis of IBD, and demonstrate the utility of trans-ethnic association studies for mapping complex disease loci and understanding genetic architecture across diverse populations. PMID:26192919

Psychopathology, temperament and unintentional injury: cross-sectional and longitudinal relationships.

PubMed

Rowe, Richard; Simonoff, Emily; Silberg, Judy L

2007-01-01

Growing evidence indicates a link between unintentional injury and both disruptive and emotional psychopathology. We present further evidence of these associations and address the underlying mechanisms. We also examine the genetic contribution to unintentional injury. The Virginia Twin Study of Adolescent Behavioral Development provides genetically informative multi-wave and multi-informant data regarding common psychopathology using the Child and Adolescent Psychiatric Assessment interview. The EASI temperament scales and child injury involvement were measured in parent-report questionnaires. Unintentional injury showed significant genetic effects in girls and significant shared environmental effects in boys and girls. Symptoms of over-anxious disorder (OAD), and the EASI temperament scales were independently associated with injury. Longitudinal modeling showed impulsivity and OAD symptoms were related prospectively to injury involvement. Injuries did not increase risk for later impulsivity or OAD symptoms but were related prospectively to separation anxiety disorder symptoms. Impulsivity and OAD symptoms increased risk of later injury. We discuss the processes that may be involved in these relationships.

Interdependence between transcription and mRNP processing and export, and its impact on genetic stability.

PubMed

Luna, Rosa; Jimeno, Sonia; Marín, Mercedes; Huertas, Pablo; García-Rubio, María; Aguilera, Andrés

2005-06-10

The conserved eukaryotic THO-TREX complex acts at the interface between transcription and mRNA export and affects transcription-associated recombination. To investigate the interdependence of nuclear mRNA processes and their impact on genomic integrity, we analyzed transcript accumulation and recombination of 40 selected mutants covering representative steps of the biogenesis and export of the messenger ribonucleoprotein particle (mRNP). None of the mutants analyzed shared the strong transcript-accumulation defect and hyperrecombination of THO mutants. Nevertheless, mutants in 3' end cleavage/polyadenylation, nuclear exosome, and mRNA export showed a weak but significant effect on recombination and transcript accumulation. Mutants of the nuclear exosome (rrp6) and 3' end processing factors (rna14 and rna15) showed inefficient transcription elongation and genetic interactions with THO. The results suggest a tight interdependence among mRNP biogenesis steps and transcription and an unexpected effect of the nuclear exosome and the cleavage/polyadenylation factors on transcription elongation and genetic integrity.

Genetic and environmental influences on adolescents' smoking involvement: a multi-informant twin study.

PubMed

Seglem, Karoline Brobakke; Waaktaar, Trine; Ask, Helga; Torgersen, Svenn

2015-03-01

Studying monozygotic and dizygotic adolescent twin pairs of both sexes reared together, the present study examined the extent to which the variance in smoking involvement is attributable to genetic and environmental effects, and to what extent there are sex differences in the etiology. Questionnaire data on how often the adolescent had ever smoked tobacco was collected from a population-based twin sample consisting of seven national birth cohorts (ages 12-18), their mothers, and their fathers (N = 1,394 families). The data was analyzed with multivariate genetic modeling, using a multi-informant design. The etiological structure of smoking involvement was best represented in an ACE common pathway model, with smoking defined as a latent factor loading onto all three informants' reports. Estimates could be set equal across sexes. Results showed that adolescent lifetime smoking involvement was moderately heritable (37 %). The largest influence was from the shared environment (56 %), while environmental effects unique to each twin had minimal influence (7 %).

A Twin Study of Spatial and Non-Spatial Delayed Response Performance in Middle Age

PubMed Central

Kremen, William S.; Mai, Tuan; Panizzon, Matthew S.; Franz, Carol E.; Blankfeld, Howard M.; Xian, Hong; Eisen, Seth A.; Tsuang, Ming T.; Lyons, Michael J.

2011-01-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h2=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (rg=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high “failure” rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. PMID:21477911

Behavioral resilience in the post-genomic era: emerging models linking genes with environment

PubMed Central

Rende, Richard

2012-01-01

One of the most important deliverables of the post-genomic era has been a new and nuanced appreciation of how the environment shapes—and holds potential to alter—the expression of susceptibility genes for behavioral dimensions and disorders. This paper will consider three themes that have emerged from cutting-edge research studies that utilize newer molecular genetic approaches as well as tried-and-true genetic epidemiological methodologies, with particular reference to evolving perspectives on resilience and plasticity. These themes are: (1) evidence for replicable and robust shared environmental effects on a number of clinically relevant behaviors in childhood and adolescence; (2) evolving research on gene-environment interaction; and (3) a newer focus on differential susceptibility and plasticity. The net sum of these themes is that consideration of genetic effects on behavioral dimensions and disorders needs to be connected to thinking about the role of environment as a potent source for promoting resilience and change. PMID:22461772

A twin study of early-childhood asthma in Puerto Ricans.

PubMed

Bunyavanich, Supinda; Silberg, Judy L; Lasky-Su, Jessica; Gillespie, Nathan A; Lange, Nancy E; Canino, Glorisa; Celedón, Juan C

2013-01-01

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood. To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤ 3 years old. 678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥ 1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age. The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%-86%), while genetic effects drove variance in all phenotypes (45%-65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility. Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.

Original Mycobacterial Sin, a consequence of highly homologous antigens?

PubMed

Jenkins, A O; Michel, A; Rutten, V

2017-05-01

The role of antigens shared between Mycobacteria in in-vivo cross-reactive immune responses in host animals, have been reported to be responsible for reduced BCG vaccination efficacy as well reduced specificity of routine immunological diagnostic tests. This presents with significant disease control challenges in humans and animals. The present review highlights the results of previous studies on the effect of pre-sensitization to environmental mycobacteria on either pathogenic mycobacteria and/or M. bovis BCG, in experimental animals. It also takes an in-depth view into assessing the genetic similarities and relationships between atypical mycobacteria and Mycobacterium tuberculosis complex (MTBC) and how they might explain the immunological imprint of environmental mycobacteria in directing the hosts' immune response upon subsequent exposure to other classes of mycobacteria. The outcome of this review suggests that genetic closeness between particular atypical mycobacteria and MTBC usually indicate a higher level of homology for certain shared protective antigens. This ultimately results in a higher level of cross reactive immune responses as compared with other atypical mycobacteria that are further away genetically. This would explain the different effects of environmental mycobacteria on MTBC that have been reported in the different studies. In other words the direction of the host immune system in response to exposure to MTBC would depend on the type of environmental mycobacteria that was encountered in the initial exposure. We also explain these mycobacterial interactions in the context of the phenomenon of "Original Mycobacterial Sin". The effects of these inevitable mycobacterial interactions on field diagnosis and control by vaccination and how to circumvent them are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Genetic contribution to patent ductus arteriosus in the premature newborn.

PubMed

Bhandari, Vineet; Zhou, Gongfu; Bizzarro, Matthew J; Buhimschi, Catalin; Hussain, Naveed; Gruen, Jeffrey R; Zhang, Heping

2009-02-01

The most common congenital heart disease in the newborn population, patent ductus arteriosus, accounts for significant morbidity in preterm newborns. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition. The objective of this study was to quantify the contribution of genetic factors to the variance in liability for patent ductus arteriosus in premature newborns. A retrospective study (1991-2006) from 2 centers was performed by using zygosity data from premature twins born at < or =36 weeks' gestational age and surviving beyond 36 weeks' postmenstrual age. Patent ductus arteriosus was diagnosed by echocardiography at each center. Mixed-effects logistic regression was used to assess the effect of specific covariates. Latent variable probit modeling was then performed to estimate the heritability of patent ductus arteriosus, and mixed-effects probit modeling was used to quantify the genetic component. We obtained data from 333 dizygotic twin pairs and 99 monozygotic twin pairs from 2 centers (Yale University and University of Connecticut). Data on chorioamnionitis, antenatal steroids, gestational age, body weight, gender, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, oxygen supplementation, and bronchopulmonary dysplasia were comparable between monozygotic and dizygotic twins. We found that gestational age, respiratory distress syndrome, and institution were significant covariates for patent ductus arteriosus. After controlling for specific covariates, genetic factors or the shared environment accounted for 76.1% of the variance in liability for patent ductus arteriosus. Preterm patent ductus arteriosus is highly familial (contributed to by genetic and environmental factors), with the effect being mainly environmental, after controlling for known confounders.

Genetic effects influencing risk for major depressive disorder in China and Europe.

PubMed

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-03-28

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log 10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genetic effects influencing risk for major depressive disorder in China and Europe

PubMed Central

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-01-01

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies. PMID:28350396

Plants as models for the study of human pathogenesis.

PubMed

Guttman, David S

2004-05-01

There are many common disease mechanisms used by bacterial pathogens of plants and humans. They use common means of attachment, secretion and genetic regulation. They share many virulence factors, such as extracellular polysaccharides and some type III secreted effectors. Plant and human innate immune systems also share many similarities. Many of these shared bacterial virulence mechanisms are homologous, but even more appear to have independently converged on a common function. This combination of homologous and analogous systems reveals conserved and critical steps in the disease process. Given these similarities, and the many experimental advantages of plant biology, including ease of replication, stringent genetic and reproductive control, and high throughput with low cost, it is proposed that plants would make excellent models for the study of human pathogenesis.