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

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.

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.

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.

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.

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.

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

PubMed

Wilkes, Michael S; Day, Frank C; Fancher, Tonya L; McDermott, Haley; Lehman, Erik; Bell, Robert A; Green, Michael J

2017-09-13

Screening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions. One hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information. PCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients. While our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics.

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.

Access and benefit sharing: Best practices for the use and exchange of invertebrate biological control agents

USDA-ARS?s Scientific Manuscript database

The Convention on Biological Diversity (CBD) acknowledges the sovereign rights that countries have over their ‘genetic resources’. The Nagoya Protocol that came into force in 2014 provides a framework for implementation of and equitable process by which access to, and sharing of benefits between don...

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.

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

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics

PubMed Central

Lee, Sandra Soo-Jin; Vernez, Simone L.; Ormond, K.E.; Granovetter, Mark

2013-01-01

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Methods: Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. Results: 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Conclusion: Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities. PMID:25562728

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics.

PubMed

Lee, Sandra Soo-Jin; Vernez, Simone L; Ormond, K E; Granovetter, Mark

2013-10-14

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.

PubMed

Hartz, Sarah M; Horton, Amy C; Oehlert, Mary; Carey, Caitlin E; Agrawal, Arpana; Bogdan, Ryan; Chen, Li-Shiun; Hancock, Dana B; Johnson, Eric O; Pato, Carlos N; Pato, Michele T; Rice, John P; Bierut, Laura J

2017-11-15

There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity. We tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to the 1000 Genomes reference panel. In each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R 2 range 0.8-3.7%; minimum p = 4 × 10 -23 ). These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

The DNA Bank: High-Security Bank Accounts to Protect and Share Your Genetic Identity.

PubMed

den Dunnen, Johan T

2015-07-01

With the cost of genome sequencing decreasing every day, DNA information has the potential of affecting the lives of everyone. Surprisingly, an individual has little knowledge about his own DNA information, can rarely access it, and has hardly any control over its use. This may result in preventable, life-threatening situations, and also significantly inhibits scientific progress. What we urgently need is a "DNA bank," a resource providing a secure personal account where, similar to a financial institution, you can store your DNA sequence. Using this private and secure DNA bank account, you govern your sequence-related business. For any genetic study performed, the data generated must be transferred (paid) to your DNA account. Using your account, you regulate access, knowing for what purpose (informed consent) and only for the genetic data you are willing to share. The DNA account ensures you are in the driver's seat, know what is known, and control what is happening with it. © 2015 WILEY PERIODICALS, INC.

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.

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

PubMed Central

Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

2016-01-01

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

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 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

The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders.

PubMed

Grant, J D; Lynskey, M T; Madden, P A F; Nelson, E C; Few, L R; Bucholz, K K; Statham, D J; Martin, N G; Heath, A C; Agrawal, A

2015-12-01

Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

PubMed Central

Martin, Jose-Ezequiel; Assassi, Shervin; Diaz-Gallo, Lina-Marcela; Broen, Jasper C.; Simeon, Carmen P.; Castellvi, Ivan; Vicente-Rabaneda, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A.; Espinosa, Gerard; Carreira, Patricia; Camps, Mayte; Sabio, Jose M.; D'alfonso, Sandra; Vonk, Madelon C.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Hunzelmann, Nicolas; Airo, Paolo; Beretta, Lorenzo; Scorza, Raffaella; Lunardi, Claudio; Van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Arianne; Denton, Christopher; Fonseca, Carmen; Tan, Filemon K.; Arnett, Frank; Zhou, Xiaodong; Reveille, John D.; Gorlova, Olga; Koeleman, Bobby P.C.; Radstake, Timothy R.D.J.; Vyse, Timothy; Mayes, Maureen D.; Alarcón-Riquelme, Marta E.; Martin, Javier

2013-01-01

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10−11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10−11, OR = 1.20) and JAZF1 (P = 1.11 × 10−8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity. PMID:23740937

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.

PubMed

Martin, Jose-Ezequiel; Assassi, Shervin; Diaz-Gallo, Lina-Marcela; Broen, Jasper C; Simeon, Carmen P; Castellvi, Ivan; Vicente-Rabaneda, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A; Espinosa, Gerard; Carreira, Patricia; Camps, Mayte; Sabio, Jose M; D'alfonso, Sandra; Vonk, Madelon C; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Hunzelmann, Nicolas; Airo, Paolo; Beretta, Lorenzo; Scorza, Raffaella; Lunardi, Claudio; Van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Arianne; Denton, Christopher; Fonseca, Carmen; Tan, Filemon K; Arnett, Frank; Zhou, Xiaodong; Reveille, John D; Gorlova, Olga; Koeleman, Bobby P C; Radstake, Timothy R D J; Vyse, Timothy; Mayes, Maureen D; Alarcón-Riquelme, Marta E; Martin, Javier

2013-10-01

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

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.

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

PubMed

Bergin, Jocilyn E; Kendler, Kenneth S

2012-08-01

Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

The KCNQ1 gene polymorphism as a shared genetic risk for rheumatoid arthritis and chronic periodontitis in Japanese adults: A pilot case-control study.

PubMed

Kobayashi, Tetsuo; Kido, Jun-Ichi; Ishihara, Yuichi; Omori, Kazuhiro; Ito, Satoshi; Matsuura, Takato; Bando, Takashi; Wada, Jun; Murasawa, Akira; Nakazono, Kiyoshi; Mitani, Akio; Takashiba, Shogo; Nagata, Toshihiko; Yoshie, Hiromasa

2018-03-01

A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated. We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped. Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP. The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults. © 2018 American Academy of Periodontology.

[Knowledge and destiny or longevity and old age: the heritage of Homo sapiens].

PubMed

Goddio, A S

1994-12-01

Several theories have been proposed to explain ageing: limitation of the number of cell divisions or Hayflick's limit, the genetic theory, the action of free radicals, immune deficiency, etc. All of these theories share several points in common: their genetic determinism or repercussions which appear to be part of the heritage of complex organisms. Progress in genetics with chromosome decoding to localise genes and genetic manipulations or control of gene expression will probably allow an increased life expectancy, perhaps in the near future.

Deadlock-free genetic scheduling algorithm for automated manufacturing systems based on deadlock control policy.

PubMed

Xing, KeYi; Han, LiBin; Zhou, MengChu; Wang, Feng

2012-06-01

Deadlock-free control and scheduling are vital for optimizing the performance of automated manufacturing systems (AMSs) with shared resources and route flexibility. Based on the Petri net models of AMSs, this paper embeds the optimal deadlock avoidance policy into the genetic algorithm and develops a novel deadlock-free genetic scheduling algorithm for AMSs. A possible solution of the scheduling problem is coded as a chromosome representation that is a permutation with repetition of parts. By using the one-step look-ahead method in the optimal deadlock control policy, the feasibility of a chromosome is checked, and infeasible chromosomes are amended into feasible ones, which can be easily decoded into a feasible deadlock-free schedule. The chromosome representation and polynomial complexity of checking and amending procedures together support the cooperative aspect of genetic search for scheduling problems strongly.

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.

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.

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.

Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

PubMed

Zuber, Verena; Marconett, Crystal N; Shi, Jianxin; Hua, Xing; Wheeler, William; Yang, Chenchen; Song, Lei; Dale, Anders M; Laplana, Marina; Risch, Angela; Witoelar, Aree; Thompson, Wesley K; Schork, Andrew J; Bettella, Francesco; Wang, Yunpeng; Djurovic, Srdjan; Zhou, Beiyun; Borok, Zea; van der Heijden, Henricus F M; de Graaf, Jacqueline; Swinkels, Dorine; Aben, Katja K; McKay, James; Hung, Rayjean J; Bikeböller, Heike; Stevens, Victoria L; Albanes, Demetrius; Caporaso, Neil E; Han, Younghun; Wei, Yongyue; Panadero, Maria Angeles; Mayordomo, Jose I; Christiani, David C; Kiemeney, Lambertus; Andreassen, Ole A; Houlston, Richard; Amos, Christopher I; Chatterjee, Nilanjan; Laird-Offringa, Ite A; Mills, Ian G; Landi, Maria Teresa

2016-12-01

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study.

PubMed

Arora, Manish; Weuve, Jennifer; Fall, Katja; Pedersen, Nancy L; Mucci, Lorelei A

2010-01-15

Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.

An Exploration of Shared Genetic Risk Factors Between Periodontal Disease and Cancers: A Prospective Co-Twin Study

PubMed Central

Arora, Manish; Weuve, Jennifer; Fall, Katja; Pedersen, Nancy L.; Mucci, Lorelei A.

2010-01-01

Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers. PMID:19969528

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.

Genome-wide Association Study of Dermatomyositis Reveals Genetic Overlap with other Autoimmune Disorders

PubMed Central

Miller, Frederick W.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O’Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.

2014-01-01

Objective To identify new genetic associations with juvenile and adult dermatomyositis (DM). Methods We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Results Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Conclusion Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. PMID:23983088

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

Inhibitory Control in Siblings Discordant for Exposure to Maternal Smoking during Pregnancy

ERIC Educational Resources Information Center

Micalizzi, Lauren; Marceau, Kristine; Brick, Leslie A.; Palmer, Rohan H.; Todorov, Alexandre A.; Heath, Andrew C.; Evans, Allison; Knopik, Valerie S.

2018-01-01

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects…

Understanding the Cognitive and Genetic Underpinnings of Procrastination: Evidence for Shared Genetic Influences with Goal Management and Executive Function Abilities

PubMed Central

Gustavson, Daniel E.; Miyake, Akira; Hewitt, John K.; Friedman, Naomi P.

2015-01-01

Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate two hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. PMID:26389573

Understanding the cognitive and genetic underpinnings of procrastination: Evidence for shared genetic influences with goal management and executive function abilities.

PubMed

Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

2015-12-01

Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate 2 hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. (c) 2015 APA, all rights reserved).

A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

PubMed Central

Zhu, Jia; Choa, Ruth E.-Y.; Guo, Michael H.; Plummer, Lacey; Buck, Cassandra; Palmert, Mark R.; Hirschhorn, Joel N.; Seminara, Stephanie B.

2015-01-01

Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. PMID:25636053

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

PubMed

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

2011-10-01

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

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.

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

PubMed Central

Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.

2011-01-01

Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027

Optimization of shared autonomy vehicle control architectures for swarm operations.

PubMed

Sengstacken, Aaron J; DeLaurentis, Daniel A; Akbarzadeh-T, Mohammad R

2010-08-01

The need for greater capacity in automotive transportation (in the midst of constrained resources) and the convergence of key technologies from multiple domains may eventually produce the emergence of a "swarm" concept of operations. The swarm, which is a collection of vehicles traveling at high speeds and in close proximity, will require technology and management techniques to ensure safe, efficient, and reliable vehicle interactions. We propose a shared autonomy control approach, in which the strengths of both human drivers and machines are employed in concert for this management. Building from a fuzzy logic control implementation, optimal architectures for shared autonomy addressing differing classes of drivers (represented by the driver's response time) are developed through a genetic-algorithm-based search for preferred fuzzy rules. Additionally, a form of "phase transition" from a safe to an unsafe swarm architecture as the amount of sensor capability is varied uncovers key insights on the required technology to enable successful shared autonomy for swarm operations.

Genetic pleiotropy explains associations between musical auditory discrimination and intelligence.

PubMed

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

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions.

Genetic Pleiotropy Explains Associations between Musical Auditory Discrimination and Intelligence

PubMed Central

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

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions. PMID:25419664

Genetic and Environmental Influences on Testosterone in Adolescents: Evidence for Sex Differences

PubMed Central

Harden, K. Paige; Kretsch, Natalie; Tackett, Jennifer L.; Tucker-Drob, Elliot M.

2015-01-01

The current study investigated the genetic and environmental etiology of individual differences in salivary testosterone during adolescence, using data from 49 pairs of monozygotic twins and 68 pairs of dizygotic twins, ages 14–19 years (M = 16.0 years). Analyses tested for sex differences in genetic and environmental influences on testosterone and its relation to pubertal development. Among adolescent males, individual differences in testosterone were substantially heritable (55%), and significantly associated with self-reported pubertal status (controlling for age) via common genetic influences. In contrast, there was no heritable variation in testosterone for females, and testosterone in females was not significantly associated with pubertal status after controlling for age. Rather, environmental influences shared by twins raised together accounted for all of the familial similarity in female testosterone (53%). This study adds to a small but growing body of research that investigates genetic influences on individual differences in behaviorally-relevant hormones. PMID:24523135

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.

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

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

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

Are people with chronic low back pain meeting the physical activity guidelines? A co-twin control study.

PubMed

Zadro, Joshua Robert; Shirley, Debra; Amorim, Anita; Pérez-Riquelme, Francisco; Ordoñana, Juan R; Ferreira, Paulo H

2017-06-01

Despite a large amount of research investigating physical activity (PA) levels in people with chronic low back pain (LBP), no study has investigated whether people with chronic LBP are meeting the World Health Organization (WHO) PA guidelines. Furthermore, with genetics and the early shared environment substantially influencing the presence of LBP and PA engagement, these factors could confound the association between LBP and PA and need to be controlled for. This study aimed to investigate the association between chronic LBP and meeting the PA guidelines, while controlling for the effects of genetics and early shared environment. This is a cross-sectional co-twin control study. A cross-sectional analysis was performed on 1,588 twins from the Murcia Twin Registry in Spain with available data on LBP and PA from the 2013 data collection wave. The exposure and outcome variables in our study were self-reported. Twins reporting a history of chronic LBP were asked follow-up questions to inform on the presence of recent LBP (within the past 4 weeks), previous LBP (no pain within the past 4 weeks), and persistent LBP (no pain-free month in the last 6 months). These were our exposure variables. Our outcome variable was meeting the WHO PA guidelines, which involved at least 75 minutes of vigorous-intensity PA, or at least 150 minutes of moderate-intensity PA per week. To investigate the association between chronic LBP and meeting the PA guidelines, we first performed a multivariate logistic regression on the total sample of twins. Co-variables entered the model if the univariate association between the co-variable, and both the exposure and the outcome reached a significance of p<.2. Second, to adjust for the influence of genetics and early shared environment, we performed a conditional multivariate logistic regression on complete twin pairs discordant for LBP. The Murcia Twin Registry is supported by Fundación Séneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08 and 15302/PHCS/10) and the Ministry of Science and Innovation, Spain (PSI11560-2009). Funding for this project has also been received from Fundación MAPFRE (2012). The authors declare that there are no conflicts of interest. There was a significant inverse association between recent LBP and meeting the PA guidelines (odds ratio [OR]=0.71, p=.034). When controlling for genetics and early shared environment, this association disappeared. There was no association between previous (OR=0.95, p=.779) or persistent LBP (OR=0.78, p=.192) and meeting the PA guidelines. Twins with recent LBP are less likely to meet the PA guidelines than those with no history of chronic LBP, highlighting the importance of incorporating PA promotion in the treatment of these individuals. Genetics and early shared environment appear to be confounding the association between LBP and PA, although this needs to be further tested in larger twin samples. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.

PubMed

Miller, Frederick W; Cooper, Robert G; Vencovský, Jiří; Rider, Lisa G; Danko, Katalin; Wedderburn, Lucy R; Lundberg, Ingrid E; Pachman, Lauren M; Reed, Ann M; Ytterberg, Steven R; Padyukov, Leonid; Selva-O'Callaghan, Albert; Radstake, Timothy R D J; Isenberg, David A; Chinoy, Hector; Ollier, William E R; O'Hanlon, Terrance P; Peng, Bo; Lee, Annette; Lamb, Janine A; Chen, Wei; Amos, Christopher I; Gregersen, Peter K

2013-12-01

To identify new genetic associations with juvenile and adult dermatomyositis (DM). We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single-nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5 × 10(-8)) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C-like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C-C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM. Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Genetic relationships among some subspecies of the Peregrine Falcon (Falco peregrinus L.), inferred from mitochondrial DNA control-region sequences

USGS Publications Warehouse

White, Clayton M.; Sonsthagen, Sarah A.; Sage, George K.; Anderson, Clifford; Talbot, Sandra L.

2013-01-01

The ability to successfully colonize and persist in diverse environments likely requires broad morphological and behavioral plasticity and adaptability, and this may partly explain why the Peregrine Falcon (Falco peregrinus) exhibits a large range of morphological characteristics across their global distribution. Regional and local differences within Peregrine Falcons were sufficiently variable that ∼75 subspecies have been described; many were subsumed, and currently 19 are generally recognized. We used sequence information from the control region of the mitochondrial genome to test for concordance between genetic structure and representatives of 12 current subspecies and from two areas where subspecies distributions overlap. Haplotypes were broadly shared among subspecies, and all geographic locales shared a widely distributed common haplotype (FalconCR2). Haplotypes were distributed in a star-like phylogeny, consistent with rapid expansion of a recently derived species, with observed genetic patterns congruent with incomplete lineage sorting and/or differential rates of evolution on morphology and neutral genetic characters. Hierarchical analyses of molecular variance did not uncover genetic partitioning at the continental level, despite strong population-level structure (FST = 0.228). Similar analyses found weak partitioning, albeit significant, among subspecies (FCT = 0.138). All reconstructions placed the hierofalcons' (Gyrfalcon [F. rusticolus] and Saker Falcon [F. cherrug]) haplotypes in a well-supported clade either basal or unresolved with respect to the Peregrine Falcon. In addition, haplotypes representing Taita Falcon (F. fasciinucha) were placed within the Peregrine Falcon clade.

More powerful haplotype sharing by accounting for the mode of inheritance.

PubMed

Ziegler, Andreas; Ewhida, Adel; Brendel, Michael; Kleensang, André

2009-04-01

The concept of haplotype sharing (HS) has received considerable attention recently, and several haplotype association methods have been proposed. Here, we extend the work of Beckmann and colleagues [2005 Hum. Hered. 59:67-78] who derived an HS statistic (BHS) as special case of Mantel's space-time clustering approach. The Mantel-type HS statistic correlates genetic similarity with phenotypic similarity across pairs of individuals. While phenotypic similarity is measured as the mean-corrected cross product of phenotypes, we propose to incorporate information of the underlying genetic model in the measurement of the genetic similarity. Specifically, for the recessive and dominant modes of inheritance we suggest the use of the minimum and maximum of shared length of haplotypes around a marker locus for pairs of individuals. If the underlying genetic model is unknown, we propose a model-free HS Mantel statistic using the max-test approach. We compare our novel HS statistics to BHS using simulated case-control data and illustrate its use by re-analyzing data from a candidate region of chromosome 18q from the Rheumatoid Arthritis (RA) Consortium. We demonstrate that our approach is point-wise valid and superior to BHS. In the re-analysis of the RA data, we identified three regions with point-wise P-values<0.005 containing six known genes (PMIP1, MC4R, PIGN, KIAA1468, TNFRSF11A and ZCCHC2) which might be worth follow-up.

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.

Disentangling privacy from property: toward a deeper understanding of genetic privacy.

PubMed

Suter, Sonia M

2004-04-01

With the mapping of the human genome, genetic privacy has become a concern to many. People care about genetic privacy because genes play an important role in shaping us--our genetic information is about us, and it is deeply connected to our sense of ourselves. In addition, unwanted disclosure of our genetic information, like a great deal of other personal information, makes us vulnerable to unwanted exposure, stigmatization, and discrimination. One recent approach to protecting genetic privacy is to create property rights in genetic information. This Article argues against that approach. Privacy and property are fundamentally different concepts. At heart, the term "property" connotes control within the marketplace and over something that is disaggregated or alienable from the self. "Privacy," in contrast, connotes control over access to the self as well as things close to, intimately connected to, and about the self. Given these different meanings, a regime of property rights in genetic information would impoverish our understanding of that information, ourselves, and the relationships we hope will be built around and through its disclosure. This Article explores our interests in genetic information in order to deepen our understanding of the ongoing discourse about the distinction between property and privacy. It develops a conception of genetic privacy with a strong relational component. We ordinarily share genetic information in the context of relationships in which disclosure is important to the relationship--family, intimate, doctor-patient, researcher-participant, employer-employee, and insurer-insured relationships. Such disclosure makes us vulnerable to and dependent on the person to whom we disclose it. As a result, trust is essential to the integrity of these relationships and our sharing of genetic information. Genetic privacy can protect our vulnerability in these relationships and enhance the trust we hope to have in them. Property, in contrast, by connoting commodification, disaggregation, and arms-length dealings, can negatively affect the self and harm these relationships. This Article concludes that a deeper understanding of genetic privacy calls for remedies for privacy violations that address dignitary harm and breach of trust, as opposed to market harms, as the property model suggests.

Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication.

PubMed

Hodgson, Jan; Metcalfe, Sylvia; Gaff, Clara; Donath, Susan; Delatycki, Martin B; Winship, Ingrid; Skene, Loane; Aitken, MaryAnne; Halliday, Jane

2016-03-01

When an inherited genetic condition is diagnosed in an individual it has implications for other family members. Privacy legislation and ethical considerations can restrict health professionals from communicating directly with other family members, and so it is frequently the responsibility of the first person in a family to receive the diagnosis (the proband) to share this news. Communication of genetic information is challenging and many at-risk family members remain unaware of important information that may be relevant to their or their children's health. We conducted a randomised controlled trial in six public hospitals to assess whether a specifically designed telephone counselling intervention improved family communication about a new genetic diagnosis. Ninety-five probands/parents of probands were recruited from genetics clinics and randomised to the intervention or control group. The primary outcome measure was the difference between the proportion of at-risk relatives who contacted genetics services for information and/or genetic testing. Audit of the family genetic file after 18 months revealed that 25.6% of intervention group relatives compared with 20.9% of control group relatives made contact with genetic services (adjusted odds ratio (OR) 1.30, 95% confidence interval 0.70-2.42, P=0.40). Although no major difference was detected overall between the intervention and control groups, there was more contact in the intervention group where the genetic condition conferred a high risk to offspring (adjusted OR 24.0, 95% confidence interval 3.4-168.5, P=0.001). The increasing sophistication and scope of genetic testing makes it imperative for health professionals to consider additional ways of supporting families in communicating genetic information.

Nurture Net of Nature: Re-Evaluating the Role of Shared Environments in Academic Achievement and Verbal Intelligence

PubMed Central

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2016-01-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods – that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. PMID:26004471

Nurture net of nature: Re-evaluating the role of shared environments in academic achievement and verbal intelligence.

PubMed

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2015-07-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods - that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. Copyright © 2015. Published by Elsevier Inc.

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 Longitudinal Analysis of Anger and Inhibitory Control in Twins from 12–36 Months of Age

PubMed Central

Goldsmith, H. Hill

2010-01-01

Inhibitory control (IC) is a dimension of child temperament that involves the self-regulation of behavioral responses under some form of instruction or expectation. Although IC is posited to appear in toddlerhood, the voluntary control of emotions such as anger begins earlier. Little research has analyzed relations between emotional development in infancy and later emerging IC. We examined phenotypic associations and genetic and environmental influences on parent-and laboratory-assessed anger and IC in a twin sample from 12 to 36 months of age. Typically, twins with low levels of IC had high levels of anger. Behavioral genetic findings confirmed significant genetic influences on anger and IC as assessed by parents, and on lab-based anger assessments. Shared environmental factors contributed to twin similarity on lab-assessed anger and IC at 36 months. Phenotypic covariance between anger and IC was largely due to overlapping genetic factors for parent ratings, and environmental factors in the laboratory. PMID:21159093

Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.

PubMed

Bodea, Corneliu A; Middleton, Frank A; Melhem, Nadine M; Klei, Lambertus; Song, Youeun; Tiobech, Josepha; Marumoto, Pearl; Yano, Victor; Faraone, Stephen V; Roeder, Kathryn; Myles-Worsley, Marina; Devlin, Bernie; Byerley, William

2017-02-01

To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlights PCDH10 , encoding a cadherin-related neuronal receptor, as possibly involved in risk.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

PubMed

Ferreira, Manuel A; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; van Dongen, Jenny; Lu, Yi; Rüschendorf, Franz; Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik K E; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-12-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10 -8 ), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

PubMed Central

Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik KE; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-01-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. To identify shared risk variants, we performed a genome-wide association study (GWAS, n=360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P<3x10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes. PMID:29083406

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes.

PubMed

Hernandez-Valladares, Maria; Rihet, Pascal; Iraqi, Fuad A

2014-01-01

There is growing evidence for human genetic factors controlling the outcome of malaria infection, while molecular basis of this genetic control is still poorly understood. Case-control and family-based studies have been carried out to identify genes underlying host susceptibility to malarial infection. Parasitemia and mild malaria have been genetically linked to human chromosomes 5q31-q33 and 6p21.3, and several immune genes located within those regions have been associated with malaria-related phenotypes. Association and linkage studies of resistance to malaria are not easy to carry out in human populations, because of the difficulty in surveying a significant number of families. Murine models have proven to be an excellent genetic tool for studying host response to malaria; their use allowed mapping 14 resistance loci, eight of them controlling parasitic levels and six controlling cerebral malaria. Once quantitative trait loci or genes have been identified, the human ortholog may then be identified. Comparative mapping studies showed that a couple of human and mouse might share similar genetically controlled mechanisms of resistance. In this way, char8, which controls parasitemia, was mapped on chromosome 11; char8 corresponds to human chromosome 5q31-q33 and contains immune genes, such as Il3, Il4, Il5, Il12b, Il13, Irf1, and Csf2. Nevertheless, part of the genetic factors controlling malaria traits might differ in both hosts because of specific host-pathogen interactions. Finally, novel genetic tools including animal models were recently developed and will offer new opportunities for identifying genetic factors underlying host phenotypic response to malaria, which will help in better therapeutic strategies including vaccine and drug development.

Longitudinal Associations Between Marital Instability and Child Sleep Problems across Infancy and Toddlerhood in Adoptive Families

PubMed Central

Mannering, Anne M.; Harold, Gordon T.; Leve, Leslie D.; Shelton, Katherine H.; Shaw, Daniel S.; Conger, Rand D.; Neiderhiser, Jenae M.; Scaramella, Laura V.; Reiss, David

2009-01-01

This study examined the longitudinal association between marital instability and child sleep problems at ages 9 and 18 months in 357 families with a genetically unrelated infant adopted at birth. This design eliminates shared genes as an explanation for similarities between parent and child. Structural equation modeling indicated that T1 marital instability predicted T2 child sleep problems, but T1 child sleep problems did not predict T2 marital instability. This pattern of results was replicated when models were estimated separately for mothers and children and for fathers and children. Thus, even after controlling for stability in sleep problems and marital instability and eliminating shared genetic influences on associations using a longitudinal adoption design, marital instability prospectively predicts early childhood sleep patterns. PMID:21557740

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

Genetic Architecture of the Variation in Male-Specific Ossified Processes on the Anal Fins of Japanese Medaka.

PubMed

Kawajiri, Maiko; Fujimoto, Shingo; Yoshida, Kohta; Yamahira, Kazunori; Kitano, Jun

2015-10-28

Traits involved in reproduction evolve rapidly and show great diversity among closely related species. However, the genetic mechanisms that underlie the diversification of courtship traits are mostly unknown. Japanese medaka fishes (Oryzias latipes) use anal fins to attract females and to grasp females during courtship; the males have longer anal fins with male-specific ossified papillary processes on the fin rays. However, anal fin morphology varies between populations: the southern populations tend to have longer anal fins and more processes than the northern populations. In the present study, we conducted quantitative trait locus (QTL) mapping to investigate the genetic architecture underlying the variation in the number of papillary processes of Japanese medaka fish and compared the QTL with previously identified QTL controlling anal fin length. First, we found that only a few QTL were shared between anal fin length and papillary process number. Second, we found that the numbers of papillary processes on different fin rays often were controlled by different QTL. Finally, we produced another independent cross and found that some QTL were repeatable between the two crosses, whereas others were specific to only one cross. These results suggest that variation in the number of papillary processes is polygenic and controlled by QTL that are distinct from those controlling anal fin length. Thus, different courtship traits in Japanese medaka share a small number of QTL and have the potential for independent evolution. Copyright © 2015 Kawajiri et al.

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.

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 influence of pathogen and host genetics on a trade-off between latent period and spore production capacity in the wheat pathogen, Puccinia triticina.

PubMed

Pariaud, Bénédicte; Berg, Femke; Bosch, Frank; Powers, Stephen J; Kaltz, Oliver; Lannou, Christian

2013-02-01

Crop pathogens are notorious for their rapid adaptation to their host. We still know little about the evolution of their life cycles and whether there might be trade-offs between fitness components, limiting the evolutionary potential of these pathogens. In this study, we explored a trade-off between spore production capacity and latent period in Puccinia triticina, a fungal pathogen causing leaf rust on wheat. Using a simple multivariate (manova) technique, we showed that the covariance between the two traits is under shared control of host and pathogen, with contributions from host genotype (57%), pathogen genotype (18.4%) and genotype × genotype interactions (12.5%). We also found variation in sign and strength of genetic correlations for the pathogen, when measured on different host varieties. Our results suggest that these important pathogen life-history traits do not freely respond to directional selection and that precise evolutionary trajectories are contingent on the genetic identity of the interacting host and pathogen.

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

Investigating genetic and environmental contributions to adolescent externalizing behavior in a collectivistic culture: a multi-informant twin study.

PubMed

Chen, J; Yu, J; Zhang, J; Li, X; McGue, M

2015-07-01

Little is known about the etiology of adolescents' externalizing behavior (Ext) in collectivistic cultures. We aimed to fill this gap by investigating the genetic and environmental influences on Ext in Chinese adolescents. The etiological heterogeneity of aggression (AGG) and rule breaking (RB) was also examined. The study sample included 908 pairs of same-sex twins aged from 10 to 18 years (mean = 13.53 years, s.d. = 2.26). Adolescents' Ext were assessed with the Achenbach System of Empirically Based Assessment including Child Behavior Checklist, Teacher Report Form, and Youth Self-Report. Univariate genetic analyses showed that genetic influences on all measures were moderate ranging from 34% to 50%, non-shared environmental effects ranged from 23% to 52%, and shared environmental effects were significant in parent- and teacher-reported measures ranging from 29% to 43%. Bivariate genetic analyses indicated that AGG and RB shared large genetic influences (r g = 0.64-0.79) but moderate non-shared environmental factors (r e = 0.34-0.52). Chinese adolescents' Ext was moderately influenced by genetic factors. AGG and RB had moderate independent genetic and non-shared environmental influences, and thus constitute etiologically distinct dimensions within Ext in Chinese adolescents. The heritability of AGG, in particular, was smaller in Chinese adolescents than suggested by previous data obtained on Western peers. This study suggests that the collectivistic cultural values and Confucianism philosophy may attenuate genetic potential in Ext, especially AGG.

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

Microgeographic Genetic Variation of the Malaria Vector Anopheles darlingi Root (Diptera: Culicidae) from Córdoba and Antioquia, Colombia

PubMed Central

Gutiérrez, Lina A.; Gómez, Giovan F.; González, John J.; Castro, Martha I.; Luckhart, Shirley; Conn, Jan E.; Correa, Margarita M.

2010-01-01

Anopheles darlingi is an important vector of Plasmodium spp. in several malaria-endemic regions of Colombia. This study was conducted to test genetic variation of An. darlingi at a microgeographic scale (approximately 100 km) from localities in Córdoba and Antioquia states, in western Colombia, to better understand the potential contribution of population genetics to local malaria control programs. Microsatellite loci: nuclear white and cytochrome oxidase subunit I (COI) gene sequences were analyzed. The northern white gene lineage was exclusively distributed in Córdoba and Antioquia and shared COI haplotypes were highly represented in mosquitoes from both states. COI analyses showed these An. darlingi are genetically closer to Central American populations than southern South American populations. Overall microsatellites and COI analysis showed low to moderate genetic differentiation among populations in northwestern Colombia. Given the existence of high gene flow between An. darlingi populations of Córdoba and Antioquia, integrated vector control strategies could be developed in this region of Colombia. PMID:20595475

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

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.

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.

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

Phenotypic and genetic associations between reading and attention-deficit/hyperactivity disorder dimensions in adolescence.

PubMed

Plourde, Vickie; Boivin, Michel; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette

2017-10-01

Multiple studies have shown that reading abilities and attention-deficit/hyperactivity disorder symptoms, mainly inattention symptoms, are phenotypically and genetically associated during childhood. However, few studies have looked at these associations during adolescence to investigate possible developmental changes. The aim of the study is to examine the genetic and environmental etiology of the associations between inattention and hyperactivity reported by parents, and reading accuracy, reading speed, and word reading in a population-based twin sample (Quebec Newborn Twin Study). Participants were between 14 and 15 years of age at the time of testing (N = 668-837). Phenotypic results showed that when nonverbal and verbal abilities were controlled, inattention, but not hyperactivity/impulsivity, was a modest and significant predictor of reading accuracy, reading speed, and word reading. The associations between inattention and all reading abilities were partly explained by genetic and unique environmental factors. However, the genetic correlations were no longer significant after controlling for verbal abilities. In midadolescence, inattention is the attention-deficit/hyperactivity disorder dimension associated with reading abilities, but they could also share genetic factors with general verbal skills.

Do shared etiological factors contribute to the relationship between sexual orientation and depression?

PubMed

Zietsch, B P; Verweij, K J H; Heath, A C; Madden, P A F; Martin, N G; Nelson, E C; Lynskey, M T

2012-03-01

Gays, lesbians and bisexuals (i.e. non-heterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by non-heterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in non-heterosexuals. A community-based sample of adult twins (n=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analyzed using the classical twin design. Non-heterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation. Non-heterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved.

Do shared etiological factors contribute to the relationship between sexual orientation and depression?

PubMed Central

Zietsch, Brendan P.; Verweij, Karin J. H.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Nelson, Elliot C.; Lynskey, Michael T.

2013-01-01

Background Gays, lesbians, and bisexuals (i.e. nonheterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by nonheterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in nonheterosexuals. Method A community-based sample of adult twins (N=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse, and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analysed using the classical twin design. Results Nonheterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression, respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation. Conclusions Nonheterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved. PMID:21867592

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

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

Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort.

PubMed

Llewellyn, Clare H; van Jaarsveld, Cornelia H M; Plomin, Robert; Fisher, Abigail; Wardle, Jane

2012-03-01

The behavioral susceptibility model proposes that inherited differences in traits such as appetite confer differential risk of weight gain and contribute to the heritability of weight. Evidence that the FTO gene may influence weight partly through its effects on appetite supports this model, but testing the behavioral pathways for multiple genes with very small effects is not feasible. Twin analyses make it possible to get a broad-based estimate of the extent of shared genetic influence between appetite and weight. The objective was to use multivariate twin analyses to test the hypothesis that associations between appetite and weight are underpinned by shared genetic effects. Data were from Gemini, a population-based birth cohort of twins (n = 4804) born in 2007. Infant weights at 3 mo were taken from the records of health professionals. Appetite was assessed at 3 mo for the milk-feeding period by using the Baby Eating Behaviour Questionnaire (BEBQ), a parent-reported measure of appetite [enjoyment of food, food responsiveness, slowness in eating (SE), satiety responsiveness (SR), and appetite size (AS)]. Multivariate quantitative genetic modeling was used to test for shared genetic influences. Significant correlations were found between all BEBQ traits and weight. Significant shared genetic influence was identified for weight with SE, SR, and AS; genetic correlations were between 0.22 and 0.37. Shared genetic effects explained 41-45% of these phenotypic associations. Differences in weight in infancy may be due partly to genetically determined differences in appetitive traits that confer differential susceptibility to obesogenic environments.

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 Factors Involved in Celiac Disease, Type 2 Diabetes and Anorexia Nervosa Suggest Common Molecular Pathways for Chronic Diseases.

PubMed

Mostowy, Joanna; Montén, Caroline; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel; Torinsson Naluai, Åsa

2016-01-01

Genome-wide association studies (GWAS) have identified several genetic regions involved in immune-regulatory mechanisms to be associated with celiac disease. Previous GWAS also revealed an over-representation of genes involved in type 2 diabetes and anorexia nervosa associated with celiac disease, suggesting involvement of common metabolic pathways for development of these chronic diseases. The aim of this study was to extend these previous analyses to study the gene expression in the gut from children with active celiac disease. Thirty six target genes involved in type 2 diabetes and four genes associated with anorexia nervosa were investigated for gene expression in small intestinal biopsies from 144 children with celiac disease at median (range) age of 7.4 years (1.6-17.8) and from 154 disease controls at a median (range) age 11.4.years (1.4-18.3). A total of eleven of genes were differently expressed in celiac patients compared with disease controls of which CD36, CD38, FOXP1, SELL, PPARA, PPARG, AGT previously associated with type 2 diabetes and AKAP6, NTNG1 with anorexia nervosa remained significant after correction for multiple testing. Shared genetic factors involved in celiac disease, type 2 diabetes and anorexia nervosa suggest common underlying molecular pathways for these diseases.

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.

The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.

PubMed

Shaw, Liam; Ribeiro, Andre L R; Levine, Adam P; Pontikos, Nikolas; Balloux, Francois; Segal, Anthony W; Roberts, Adam P; Smith, Andrew M

2017-09-12

The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. Copyright © 2017 Shaw et al.

Shared atypical default mode and salience network functional connectivity between autism and schizophrenia.

PubMed

Chen, Heng; Uddin, Lucina Q; Duan, Xujun; Zheng, Junjie; Long, Zhiliang; Zhang, Youxue; Guo, Xiaonan; Zhang, Yan; Zhao, Jingping; Chen, Huafu

2017-11-01

Schizophrenia and autism spectrum disorder (ASD) are two prevalent neurodevelopmental disorders sharing some similar genetic basis and clinical features. The extent to which they share common neural substrates remains unclear. Resting-state fMRI data were collected from 35 drug-naïve adolescent participants with first-episode schizophrenia (15.6 ± 1.8 years old) and 31 healthy controls (15.4 ± 1.6 years old). Data from 22 participants with ASD (13.1 ± 3.1 years old) and 21 healthy controls (12.9 ± 2.9 years old) were downloaded from the Autism Brain Imaging Data Exchange. Resting-state functional networks were constructed using predefined regions of interest. Multivariate pattern analysis combined with multi-task regression feature selection methods were conducted in two datasets separately. Classification between individuals with disorders and controls was achieved with high accuracy (schizophrenia dataset: accuracy = 83%; ASD dataset: accuracy = 80%). Shared atypical brain connections contributing to classification were mostly present in the default mode network (DMN) and salience network (SN). These functional connections were further related to severity of social deficits in ASD (p = 0.002). Distinct atypical connections were also more related to the DMN and SN, but showed different atypical connectivity patterns between the two disorders. These results suggest some common neural mechanisms contributing to schizophrenia and ASD, and may aid in understanding the pathology of these two neurodevelopmental disorders. Autism Res 2017, 10: 1776-1786. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism spectrum disorder (ASD) and schizophrenia are two common neurodevelopmental disorders which share several genetic and behavioral features. The present study identified common neural mechanisms contributing to ASD and schizophrenia using resting-state functional MRI data. The results may help to understand the pathology of these two neurodevelopmental disorders. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Genetic and Environmental Influences on Pulmonary Function and Muscle Strength: The Chinese Twin Study of Aging.

PubMed

Tian, Xiaocao; Xu, Chunsheng; Wu, Yili; Sun, Jianping; Duan, Haiping; Zhang, Dongfeng; Jiang, Baofa; Pang, Zengchang; Li, Shuxia; Tan, Qihua

2017-02-01

Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin modeling on FEV1, FVC, handgrip, and FTSST in 379 twin pairs (240 MZ and 139 DZ) with median age of 50 years (40-80 years). Data were analyzed by fitting univariate and bivariate twin models to estimate the genetic and environmental influences on these measures of physical function. Heritability was moderate for FEV1, handgrip, and FTSST (55-60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique environment (40-50%). Bivariate analysis showed highly positive genetic correlations between FEV1 and FVC (r G = 1.00), and moderately negative genetic correlations between FTSST and FEV1 (r G = -0.33) and FVC (r G = -0.42). FEV1 and FVC, as well as FEV1 and handgrip, displayed high common environmental correlations (r C = 1.00), and there were moderate correlations between FVC and handgrip (r C = 0.44). FEV1 and FVC showed high unique environmental correlations (r E = 0.76) and low correlations between handgrip and FEV1 (r E = 0.17), FVC (r E = 0.14), and FTSST (r E = -0.13) with positive or negative direction. We conclude that genetic factors contribute significantly to the individual differences in common indicators of daily functioning (FEV1, handgrip, and FTSST). FEV1 and FVC were genetically and environmentally correlated. Pulmonary function and FTSST may share similar sets of genes but in the negative direction. Pulmonary function and muscle strength may have a shared environmental background.

Longitudinal associations between marital instability and child sleep problems across infancy and toddlerhood in adoptive families.

PubMed

Mannering, Anne M; Harold, Gordon T; Leve, Leslie D; Shelton, Katherine H; Shaw, Daniel S; Conger, Rand D; Neiderhiser, Jenae M; Scaramella, Laura V; Reiss, David

2011-01-01

This study examined the longitudinal association between marital instability and child sleep problems at ages 9 and 18 months in 357 families with a genetically unrelated infant adopted at birth. This design eliminates shared genes as an explanation for similarities between parent and child. Structural equation modeling indicated that T1 marital instability predicted T2 child sleep problems, but T1 child sleep problems did not predict T2 marital instability. This result was replicated when models were estimated separately for mothers and fathers. Thus, even after controlling for stability in sleep problems and marital instability and eliminating shared genetic influences on associations using a longitudinal adoption design, marital instability prospectively predicts early childhood sleep patterns. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

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.

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…

Genetic Variability of the Grey Wolf Canis lupus in the Caucasus in Comparison with Europe and the Middle East: Distinct or Intermediary Population?

PubMed Central

Pilot, Małgorzata; Dąbrowski, Michał J.; Hayrapetyan, Vahram; Yavruyan, Eduard G.; Kopaliani, Natia; Tsingarska, Elena; Bujalska, Barbara; Kamiński, Stanisław; Bogdanowicz, Wiesław

2014-01-01

Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population – a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems. PMID:24714198

Open-source, community-driven microfluidics with Metafluidics.

PubMed

Kong, David S; Thorsen, Todd A; Babb, Jonathan; Wick, Scott T; Gam, Jeremy J; Weiss, Ron; Carr, Peter A

2017-06-07

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. We use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.

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.

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

PubMed Central

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Cardona Silgado, Julio C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Walkup, John; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G.M.; Yao, Yin; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

2014-01-01

Obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS) are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. Here, we report a combined genome-wide association study (GWAS) of TS and OCD in 2723 cases (1310 with OCD, 834 with TS, 579 with OCD plus TS/chronic tics (CT)), 5667 ancestry-matched controls, and 290 OCD parent-child trios. Although no individual single nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels, i.e. expression quantitative loci (eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10−4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, TS had a smaller, non-significant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and TS/CT were included in the analysis (p=0.01). Previous work has shown that TS and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of TS and OCD. Furthermore, OCD with co-occurring TS/CT may have different underlying genetic susceptibility compared to OCD alone. PMID:25158072

Are there common familial influences for major depressive disorder and an overeating-binge eating dimension in both European American and African American female twins?

PubMed

Munn-Chernoff, Melissa A; Grant, Julia D; Agrawal, Arpana; Koren, Rachel; Glowinski, Anne L; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C; Duncan, Alexis E

2015-05-01

Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg  = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re  = .26 [.09, .42]). Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups. © 2014 Wiley Periodicals, Inc.

Are There Common Familial Influences for Major Depressive Disorder and an Overeating-Binge Eating Dimension in both European-American and African-American Female Twins?

PubMed Central

Munn-Chernoff, Melissa A.; Grant, Julia D.; Agrawal, Arpana; Koren, Rachel; Glowinski, Anne L.; Bucholz, Kathleen K.; Madden, Pamela A. F.; Heath, Andrew C.; Duncan, Alexis E.

2014-01-01

Objective Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE), phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups Method Participants included 3226 European-American (EA) and 550 African-American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. Results The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re = .26 [.09, .42]) Discussion Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups. PMID:24659561

Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD.

PubMed

Stergiakouli, Evie; Martin, Joanna; Hamshere, Marian L; Langley, Kate; Evans, David M; St Pourcain, Beate; Timpson, Nicholas J; Owen, Michael J; O'Donovan, Michael; Thapar, Anita; Davey Smith, George

2015-04-01

Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample. Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample. Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08-1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04-0.54], p = 0.02), and symptom domain severity in the clinical sample. This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Extending the ‘cross-disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

PubMed Central

McGrath, Lauren M.; Braaten, Ellen B.; Doty, Nathan D.; Willoughby, Brian L.; Wilson, H. Kent; O’Donnell, Ellen H.; Colvin, Mary K.; Ditmars, Hillary L.; Blais, Jessica E.; Hill, Erin N.; Metzger, Aaron; Perlis, Roy H.; Willcutt, Erik G.; Smoller, Jordan W.; Waldman, Irwin D.; Faraone, Stephen V.; Seidman, Larry J.; Doyle, Alysa E.

2016-01-01

Background Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with ‘cross-disorder’ relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. Methods Data are from 393 participants, ages 8 to 17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of autism spectrum disorder, bipolar illness and schizophrenia, including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively. Results We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting it related to a general increase in psychopathology symptoms across those dimensions. Conclusions Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relate to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability. PMID:26411927

Resistance patterns, ESBL genes, and genetic relatedness of Escherichia coli from dogs and owners

PubMed Central

Carvalho, A.C.; Barbosa, A.V.; Arais, L.R.; Ribeiro, P.F.; Carneiro, V.C.; Cerqueira, A.M.F.

2016-01-01

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n = 134), their owners (n = 134), and humans who claim to have no contact with dogs (n = 44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains. PMID:26887238

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.

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.

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.

Peer Network Drinking Predicts Increased Alcohol Use From Adolescence to Early Adulthood After Controlling for Genetic and Shared Environmental Selection

PubMed Central

Cruz, Jennifer E.; Emery, Robert E.; Turkheimer, Eric

2013-01-01

Research consistently links adolescents' and young adults' drinking with their peers' alcohol intake. In interpreting this correlation, 2 essential questions are often overlooked. First, which peers are more important, best friends or broader social networks? Second, do peers cause increased drinking, or do young people select friends whose drinking habits match their own? The present study combines social network analyses with family (twin and sibling) designs to answer these questions via data from the National Longitudinal Study of Adolescent Health. Analysis of peer nomination data from 134 schools (n = 82,629) and 1,846 twin and sibling pairs shows that peer network substance use predicts changes in drinking from adolescence into young adult life even after controlling for genetic and shared environmental selection, as well as best friend substance use. This effect was particularly strong for high-intensity friendships. Although the peer-adolescent drinking correlation is partially explained by selection, the present finding offers powerful evidence that peers also cause increased drinking. PMID:22390657

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

Sequence analysis of the mitochondrial DNA control region of ciscoes (genus Coregonus): taxonomic implications for the Great Lakes species flock.

PubMed

Reed, K M; Dorschner, M O; Todd, T N; Phillips, R B

1998-09-01

Sequence variation in the control region (D-loop) of the mitochondrial DNA (mtDNA) was examined to assess the genetic distinctiveness of the shortjaw cisco (Coregonus zenithicus). Individuals from within the Great Lakes Basin as well as inland lakes outside the basin were sampled. DNA fragments containing the entire D-loop were amplified by PCR from specimens of C. zenithicus and the related species C. artedi, C. hoyi, C. kiyi, and C. clupeaformis. DNA sequence analysis revealed high similarity within and among species and shared polymorphism for length variants. Based on this analysis, the shortjaw cisco is not genetically distinct from other cisco species.

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

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

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.

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.

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.

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.

Strong Genetic Overlap Between Executive Functions and Intelligence

PubMed Central

Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

2016-01-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7-15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically-mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. PMID:27359131

How ownership rights over microorganisms affect infectious disease control and innovation: A root-cause analysis of barriers to data sharing as experienced by key stakeholders.

PubMed

Ribeiro, Carolina Dos S; van Roode, Martine Y; Haringhuizen, George B; Koopmans, Marion P; Claassen, Eric; van de Burgwal, Linda H M

2018-01-01

Genetic information of pathogens is an essential input for infectious disease control, public health and for research. Efficiency in preventing and responding to global outbreaks relies on timely access to such information. Still, ownership barriers stand in the way of timely sharing of genetic data from pathogens, frustrating efficient public health responses and ultimately the potential use of such resources in innovations. Under a One Health approach, stakeholders, their interests and ownership issues are manifold and need to be investigated. We interviewed key actors from governmental and non-governmental bodies to identify overlapping and conflicting interests, and the overall challenges for sharing pathogen data, to provide essential inputs to the further development of political and practical strategies for improved data sharing practices. To identify and prioritize barriers, 52 Key Opinion Leaders were interviewed. A root-cause analysis was performed to identify causal relations between barriers. Finally, barriers were mapped to the innovation cycle reflecting how they affect the range of surveillance, innovation, and sharing activities. Four main barrier categories were found: compliance to regulations, negative consequences, self-interest, and insufficient incentives for compliance. When grouped in sectors (research institutes, public health organizations, supra-national organizations and industry) stakeholders appear to have similar interests, more than when grouped in domains (human, veterinary and food). Considering the innovation process, most of barriers could be mapped to the initial stages of the innovation cycle as sampling and sequencing phases. These are stages of primary importance to outbreak control and public health response. A minority of barriers applied to later stages in the innovation cycle, which are of more importance to product development. Overall, barriers are complex and entangled, due to the diversity of causal factors and their crosscutting features. Therefore, barriers must be addressed in a comprehensive and integrated manner. Stakeholders have different interests highlighting the diversity in motivations for sharing pathogen data: prioritization of public health, basic research, economic welfare and/or innovative capacity. Broad inter-sectorial discussions should start with the alignment of these interests within sectors. The improved sharing of pathogen data, especially in upstream phases of the innovation process, will generate substantial public health benefits through increased availability of data to inform surveillance systems, as well as to allow the (re-)use of data for the development of medical countermeasures to control infectious diseases.

How ownership rights over microorganisms affect infectious disease control and innovation: A root-cause analysis of barriers to data sharing as experienced by key stakeholders

PubMed Central

Haringhuizen, George B.; Koopmans, Marion P.; Claassen, Eric; van de Burgwal, Linda H. M.

2018-01-01

Background Genetic information of pathogens is an essential input for infectious disease control, public health and for research. Efficiency in preventing and responding to global outbreaks relies on timely access to such information. Still, ownership barriers stand in the way of timely sharing of genetic data from pathogens, frustrating efficient public health responses and ultimately the potential use of such resources in innovations. Under a One Health approach, stakeholders, their interests and ownership issues are manifold and need to be investigated. We interviewed key actors from governmental and non-governmental bodies to identify overlapping and conflicting interests, and the overall challenges for sharing pathogen data, to provide essential inputs to the further development of political and practical strategies for improved data sharing practices. Methods & findings To identify and prioritize barriers, 52 Key Opinion Leaders were interviewed. A root-cause analysis was performed to identify causal relations between barriers. Finally, barriers were mapped to the innovation cycle reflecting how they affect the range of surveillance, innovation, and sharing activities. Four main barrier categories were found: compliance to regulations, negative consequences, self-interest, and insufficient incentives for compliance. When grouped in sectors (research institutes, public health organizations, supra-national organizations and industry) stakeholders appear to have similar interests, more than when grouped in domains (human, veterinary and food). Considering the innovation process, most of barriers could be mapped to the initial stages of the innovation cycle as sampling and sequencing phases. These are stages of primary importance to outbreak control and public health response. A minority of barriers applied to later stages in the innovation cycle, which are of more importance to product development. Conclusion Overall, barriers are complex and entangled, due to the diversity of causal factors and their crosscutting features. Therefore, barriers must be addressed in a comprehensive and integrated manner. Stakeholders have different interests highlighting the diversity in motivations for sharing pathogen data: prioritization of public health, basic research, economic welfare and/or innovative capacity. Broad inter-sectorial discussions should start with the alignment of these interests within sectors. The improved sharing of pathogen data, especially in upstream phases of the innovation process, will generate substantial public health benefits through increased availability of data to inform surveillance systems, as well as to allow the (re-)use of data for the development of medical countermeasures to control infectious diseases. PMID:29718947

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

PubMed

Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L

2015-01-01

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

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

HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease.

PubMed

Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P

2014-10-01

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does Education Lower Allostatic Load? A Co-twin Control Study

PubMed Central

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

2016-01-01

Many studies have found that education is associated with better health, but the causal basis of this association is unclear. The current study used a co-twin control design to examine if differences in years of education within twin pairs predict allostatic load. The strength of this design is that it controls for genetic and other familial confounds shared between twins. The sample consisted of 381 twins (with 292 twins from 146 complete pairs; mean age=57; 61% female) who participated in the biomarker project of the Midlife Development in the United States (MIDUS) study. Individual-level analyses showed a significant, negative association between years of education and allostatic load, but this association was explained entirely by familial influences shared between twins. The results of this study suggest that schooling does not itself protect against allostatic load. PMID:26778778

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.

True grit and genetics: predicting academic achievement from personality

PubMed Central

Rimfeld, Kaili; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

2015-01-01

Grit -- perseverance and passion for long-term goals -- has been shown to be a significant predictor of academic success, even after controlling for other personality factors. Here, for the first time, we use a UK-representative sample and a genetically sensitive design to unpack the etiology of grit and its prediction of academic achievement in comparison to well-established personality traits. For 4,642 16-year-olds (2,321 twin pairs), we used the Grit-S scale (Perseverance of Effort and Consistency of Interest), along with the Big-5 personality traits, to predict scores on the General Certificate of Secondary Education (GCSE) exams, which are administered UK-wide at the end of compulsory education. Twin analyses of Grit Perseverance yielded a heritability estimate of 37% (20% for Consistency of Interest) and no evidence for shared environmental influence. Personality, primarily Conscientiousness, predicts about 6% of the variance in GCSE scores, but Grit adds little to this prediction. Moreover, multivariate twin analyses showed that roughly two-thirds of the GCSE prediction is mediated genetically. Grit Perseverance of Effort and Big-5 Conscientiousness are to a large extent the same trait both phenotypically (r=0.53) and genetically (genetic correlation = 0. 86). We conclude that the etiology of Grit is highly similar to other personality traits, not only in showing substantial genetic influence but also in showing no influence of shared environmental factors. Personality significantly predicts academic achievement, but Grit adds little phenotypically or genetically to the prediction of academic achievement beyond traditional personality factors, especially Conscientiousness. PMID:26867111

Social Experiences in Kindergarten and Academic Achievement in Grade 1: A Monozygotic Twin Difference Study

ERIC Educational Resources Information Center

Vitaro, Frank; Boivin, Michel; Brendgen, Mara; Girard, Alain; Dionne, Ginette

2012-01-01

The goal of this study was to examine how different types of social experiences in kindergarten relate to Grade 1 academic achievement, while controlling for possible genetic and shared environmental influences through the use of the monozygotic (MZ) twin difference method. Social experiences in kindergarten included relationship quality with the…

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.

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

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.

Genetics of schizophrenia and smoking: an approach to studying their comorbidity based on epidemiological findings

PubMed Central

de Leon, Jose; Diaz, Francisco J.

2012-01-01

The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses. PMID:22190153

Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.

PubMed

Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J

2014-12-01

Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p < 0.05). Subjects willing-to-pay a higher amount were male, more educated, had greater cancer worry, fewer relatives with colorectal cancer, and more positive attitudes toward genetic testing (all p < 0.05). Individuals seeking risk assessment are willing-to-pay out-of-pocket for genetic testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.

Cost sharing and hereditary cancer risk: Predictors of willingness-to-pay for genetic testing

PubMed Central

Matro, Jennifer M.; Ruth, Karen J.; Wong, Yu-Ning; McCully, Katen C.; Rybak, Christina M.; Meropol, Neal J.; Hall, Michael J.

2015-01-01

Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals’ willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25–$2000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤200 vs. ≥$500). All statistical tests are two-sided (α=0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p<0.05). Subjects willing-to-pay a higher amount were male, more educated, had greater cancer worry, fewer relatives with colorectal cancer, and more positive attitudes toward genetic testing (all p<0.05). Individuals seeking risk assessment are willing-to-pay out-of-pocket for genetic testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care. PMID:24794065

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.

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 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

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

PubMed

van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

2016-07-14

Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.

Preeclampsia does not share common risk alleles in 9p21 with coronary artery disease and type 2 diabetes.

PubMed

Kaartokallio, Tea; Lokki, A Inkeri; Peterson, Hanna; Kivinen, Katja; Hiltunen, Leena; Salmela, Elina; Lappalainen, Tuuli; Maanselkä, Paula; Heino, Sanna; Knuutila, Sakari; Sayed, Ayat; Poston, Lucilla; Brennecke, Shaun P; Johnson, Matthew P; Morgan, Linda; Moses, Eric K; Kere, Juha; Laivuori, Hannele

2016-08-01

Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia. We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets. Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts. Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia. Key Message Chromosome 9p21 is not associated with preeclampsia.

Sequence analysis of the mitochondrial DNA control region of ciscoes (genus Coregonus): Taxonomic implications for the Great Lakes species flock

USGS Publications Warehouse

Reed, Kent M.; Dorschner, Michael O.; Todd, Thomas N.; Phillips, Ruth B.

1998-01-01

Sequence variation in the control region (D-loop) of the mitochondrial DNA (mtDNA) was examined to assess the genetic distinctiveness of the shortjaw cisco (Coregonus zenithicus). Individuals from within the Great Lakes Basin as well as inland lakes outside the basin were sampled. DNA fragments containing the entire D-loop were amplified by PCR from specimens ofC. zenithicus and the related species C. artedi, C. hoyi, C. kiyi, and C. clupeaformis. DNA sequence analysis revealed high similarity within and among species and shared polymorphism for length variants. Based on this analysis, the shortjaw cisco is not genetically distinct from other cisco species.

Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): Comparison to the General Population, and Genetic Structure Analysis

PubMed Central

Garcia, Danilo; Lundström, Sebastian; Brändström, Sven; Råstam, Maria; Cloninger, C. Robert; Kerekes, Nóra; Nilsson, Thomas; Anckarsäter, Henrik

2013-01-01

Background The Child and Adolescent Twin Study in Sweden (CATSS) is an on-going, large population-based longitudinal twin study. We aimed (1) to investigate the reliability of two different versions (125-items and 238-items) of Cloninger's Temperament and Character Inventory (TCI) used in the CATSS and the validity of extracting the short version from the long version, (2) to compare these personality dimensions between twins and adolescents from the general population, and (3) to investigate the genetic structure of Cloninger's model. Method Reliability and correlation analyses were conducted for both TCI versions, 2,714 CATSS-twins were compared to 631 adolescents from the general population, and the genetic structure was investigated through univariate genetic analyses, using a model-fitting approach with structural equation-modeling techniques based on same-sex twin pairs from the CATSS (423 monozygotic and 408 dizygotic pairs). Results The TCI scores from the short and long versions showed comparable reliability coefficients and were strongly correlated. Twins scored about half a standard deviation higher in the character scales. Three of the four temperament dimensions (Novelty Seeking, Harm Avoidance, and Persistence) had strong genetic and non-shared environmental effects, while Reward Dependence and the three character dimensions had moderate genetic effects, and both shared and non-shared environmental effects. Conclusions Twins showed higher scores in character dimensions compared to adolescents from the general population. At least among adolescents there is a shared environmental influence for all of the character dimensions, but only for one of the temperament dimensions (i.e., Reward Dependence). This specific finding regarding the existence of shared environmental factors behind the character dimensions in adolescence, together with earlier findings showing a small shared environmental effects on character among young adults and no shared environmental effects on character among adults, suggest that there is a shift in type of environmental influence from adolescence to adulthood regarding character. PMID:23940581

Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records.

PubMed

Darcy, Diana C; Lewis, Eleanor T; Ormond, Kelly E; Clark, David J; Trafton, Jodie A

2011-11-02

Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results. As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use. This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications.

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

Resistance patterns, ESBL genes, and genetic relatedness of Escherichia coli from dogs and owners.

PubMed

Carvalho, A C; Barbosa, A V; Arais, L R; Ribeiro, P F; Carneiro, V C; Cerqueira, A M F

2016-01-01

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n=134), their owners (n=134), and humans who claim to have no contact with dogs (n=44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Genetic control of juvenile growth and botanical architecture in an ornamental woody plant, Prunus mume Sieb. et Zucc. as revealed by a high-density linkage map.

PubMed

Sun, Lidan; Wang, Yaqun; Yan, Xiaolan; Cheng, Tangren; Ma, Kaifeng; Yang, Weiru; Pan, Huitang; Zheng, Chengfei; Zhu, Xuli; Wang, Jia; Wu, Rongling; Zhang, Qixiang

2014-01-01

Mei, Prunus mume Sieb. et Zucc., is an ornamental plant popular in East Asia and, as an important member of genus Prunus, has played a pivotal role in systematic studies of the Rosaceae. However, the genetic architecture of botanical traits in this species remains elusive. This paper represents the first genome-wide mapping study of quantitative trait loci (QTLs) that affect stem growth and form, leaf morphology and leaf anatomy in an intraspecific cross derived from two different mei cultivars. Genetic mapping based on a high-density linkage map constricted from 120 SSRs and 1,484 SNPs led to the detection of multiple QTLs for each trait, some of which exert pleiotropic effects on correlative traits. Each QTL explains 3-12% of the phenotypic variance. Several leaf size traits were found to share common QTLs, whereas growth-related traits and plant form traits might be controlled by a different set of QTLs. Our findings provide unique insights into the genetic control of tree growth and architecture in mei and help to develop an efficient breeding program for selecting superior mei cultivars.

Causes of individual differences in adolescent optimism: a study in Dutch twins and their siblings.

PubMed

Mavioğlu, Rezan Nehir; Boomsma, Dorret I; Bartels, Meike

2015-11-01

The aim of this study was to investigate the degree to which genetic and environmental influences affect variation in adolescent optimism. Optimism (3 items and 6 items approach) and pessimism were assessed by the Life Orientation Test-Revised (LOT-R) in 5,187 adolescent twins and 999 of their non-twin siblings from the Netherlands Twin Register (NTR). Males reported significantly higher optimism scores than females, while females score higher on pessimism. Genetic structural equation modeling revealed that about one-third of the variance in optimism and pessimism was due to additive genetic effects, with the remaining variance being explained by non-shared environmental effects. A bivariate correlated factor model revealed two dimensions with a genetic correlation of -.57 (CI -.67, -.47), while the non-shared environmental correlation was estimated to be -.21 (CI -.25, -.16). Neither an effect of shared environment, non-additive genetic influences, nor quantitative sex differences was found for both dimensions. This result indicates that individual differences in adolescent optimism are mainly accounted for by non-shared environmental factors. These environmental factors do not contribute to the similarity of family members, but to differences between them. Familial resemblance in optimism and pessimism assessed in adolescents is fully accounted for by genetic overlap between family members.

Aetiology for the covariation between combined type ADHD and reading difficulties in a family study: the role of IQ

PubMed Central

Cheung, Celeste H.M.; Wood, Alexis C.; Paloyelis, Yannis; Arias-Vasquez, Alejandro; Buitelaar, Jan K.; Franke, Barbara; Miranda, Ana; Mulas, Fernando; Rommelse, Nanda; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.; Faraone, Stephen V.; Asherson, Philip; Kuntsi, Jonna

2012-01-01

Background Twin studies using both clinical and population-based samples suggest that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalizability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. We therefore investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs. Methods We ran multivariate familial models on data from 1789 individuals at ages 6 to 19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC-III / WAIS-III). Results Significant phenotypic (0.2–0.4) and familial (0.3–0.5) correlations were observed among ADHD, reading difficulties and IQ. Yet 53% to 72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ. Conclusions Our finding that familial influences shared with general cognitive ability, though present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population-based study to a clinically-ascertained sample with combined type ADHD. PMID:22324316

EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort.

PubMed

Isaksson, Johan; Tammimies, Kristiina; Neufeld, Janina; Cauvet, Élodie; Lundin, Karl; Buitelaar, Jan K; Loth, Eva; Murphy, Declan G M; Spooren, Will; Bölte, Sven

2018-01-01

EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.

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 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

Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation.

PubMed

Xia, Charley; Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Hastie, Nicholas D; Hayward, Caroline; Vitart, Veronique; Navarro, Pau; Haley, Chris S

2016-02-01

Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors.

On the Genetic and Environmental Correlations between Trait Emotional Intelligence and Vocational Interest Factors.

PubMed

Schermer, Julie Aitken; Petrides, Konstantinos V; Vernon, Philip A

2015-04-01

The phenotypic (observed), genetic, and environmental correlations were examined in a sample of adult twins between the four factors and global score of the trait emotional intelligence questionnaire (TEIQue) and the seven vocational interest factors of the Jackson Career Explorer (JCE). Multiple significant correlations were found involving the work style vocational interest factor (consisting of job security, stamina, accountability, planfulness, and interpersonal confidence) and the social vocational interest factor (which included interests in the social sciences, personal services, teaching, social services, and elementary education), both of which correlated significantly with all of the TEIQue variables (well-being, self-control, emotionality, sociability, and global trait EI). Following bivariate genetic analyses, most of the significant phenotypic correlations were found to also have significant genetic correlations as well as significant non-shared (unique) environmental correlations.

Strong genetic overlap between executive functions and intelligence.

PubMed

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, 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.

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

PubMed Central

Gupta, Aditi; Juyal, Garima; Sood, Ajit; Midha, Vandana; Yamazaki, Keiko; Vich Vila, Arnau; Esaki, Motohiro; Matsui, Toshiyuki; Takahashi, Atsushi; Kubo, Michiaki; Weersma, Rinse K; Thelma, B K

2017-01-01

The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case–control genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P=1.73 × 10−10) and Japanese (P=2.02 × 10−12) but not in the Dutch. Further, a three-marker haplotype was shared between north Indians and Japanese (P<10−8), but a different five-marker haplotype was associated (P=2.07 × 10−6) in the Dutch. Of the 22 SLC44A4 SNPs, rs2736428 (novel ulcerative colitis GWAS SNP) was found significantly associated in north Indians (P=4.94 × 10−10) and Japanese (P=3.37 × 10−9), but not among the Dutch. These results suggest (i) apparent allelic heterogeneity in CFB and genetic heterogeneity in SLC44A4 across different ethnic groups; (ii) shared ulcerative colitis genetic etiological factors among Asians; and finally (iii) re-exploration of GWAS findings together with high-density genotyping/sequencing and trans-ethnic fine mapping approaches may help identify shared and population-specific risk variants and enable to explain missing disease heritability. PMID:27759029

Genetic structure of South African Nguni (Zulu) sheep populations reveals admixture with exotic breeds.

PubMed

Selepe, Mokhethi Matthews; Ceccobelli, Simone; Lasagna, Emiliano; Kunene, Nokuthula Winfred

2018-01-01

The population of Zulu sheep is reported to have declined by 7.4% between 2007 and 2011 due to crossbreeding. There is insufficient information on the genetic diversity of the Zulu sheep populations in the different area of KwaZulu Natal where they are reared. The study investigated genetic variation and genetic structure within and among eight Zulu sheep populations using 26 microsatellite markers. In addition, Damara, Dorper and South African Merino breeds were included to assess the genetic relationship between these breeds and the Zulu sheep. The results showed that there is considerable genetic diversity among the Zulu sheep populations (expected heterozygosity ranging from 0.57 to 0.69) and the level of inbreeding was not remarkable. The structure analysis results revealed that Makhathini Research Station and UNIZULU research station share common genetic structure, while three populations (Nongoma, Ulundi and Nquthu) had some admixture with the exotic Dorper breed. Thus, there is a need for sustainable breeding and conservation programmes to control the gene flow, in order to stop possible genetic dilution of the Zulu sheep.

Genetic structure of South African Nguni (Zulu) sheep populations reveals admixture with exotic breeds

PubMed Central

Kunene, Nokuthula Winfred

2018-01-01

The population of Zulu sheep is reported to have declined by 7.4% between 2007 and 2011 due to crossbreeding. There is insufficient information on the genetic diversity of the Zulu sheep populations in the different area of KwaZulu Natal where they are reared. The study investigated genetic variation and genetic structure within and among eight Zulu sheep populations using 26 microsatellite markers. In addition, Damara, Dorper and South African Merino breeds were included to assess the genetic relationship between these breeds and the Zulu sheep. The results showed that there is considerable genetic diversity among the Zulu sheep populations (expected heterozygosity ranging from 0.57 to 0.69) and the level of inbreeding was not remarkable. The structure analysis results revealed that Makhathini Research Station and UNIZULU research station share common genetic structure, while three populations (Nongoma, Ulundi and Nquthu) had some admixture with the exotic Dorper breed. Thus, there is a need for sustainable breeding and conservation programmes to control the gene flow, in order to stop possible genetic dilution of the Zulu sheep. PMID:29698497

Testing the effects of adolescent alcohol use on adult conflict-related theta dynamics.

PubMed

Harper, Jeremy; Malone, Stephen M; Iacono, William G

2017-11-01

Adolescent alcohol use (AAU) is associated with brain anomalies, but less is known about long-term neurocognitive effects. Despite theoretical models linking AAU to diminished cognitive control, empirical work testing this relationship with specific cognitive control neural correlates (e.g., prefrontal theta-band EEG dynamics) remains scarce. A longitudinal twin design was used to test the hypothesis that greater AAU is associated with reduced conflict-related EEG theta-band dynamics in adulthood, and to examine the genetic/environmental etiology of this association. In a large (N=718) population-based prospective twin sample, AAU was assessed at ages 11/14/17. Twins completed a flanker task at age 29 to elicit EEG theta-band medial frontal cortex (MFC) power and medial-dorsal prefrontal cortex (MFC-dPFC) connectivity. Two complementary analytic methods (cotwin control analysis; biometric modeling) were used to disentangle the genetic/shared environmental risk towards AAU from possible alcohol exposure effects on theta dynamics. AAU was negatively associated with adult cognitive control-related theta-band MFC power and MFC-dPFC functional connectivity. Genetic influences primarily underlie these associations. Findings provide strong evidence that genetic factors underlie the comorbidity between AAU and diminished cognitive control-related theta dynamics in adulthood. Conflict-related theta-band dynamics appear to be candidate brain-based endophenotypes/mechanisms for AAU. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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.

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

PubMed Central

Supple, Megan A.; Hines, Heather M.; Dasmahapatra, Kanchon K.; Lewis, James J.; Nielsen, Dahlia M.; Lavoie, Christine; Ray, David A.; Salazar, Camilo; McMillan, W. Owen; Counterman, Brian A.

2013-01-01

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations. PMID:23674305

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.

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.

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.

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.

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

PubMed

Hobbs, Brian D; de Jong, Kim; Lamontagne, Maxime; Bossé, Yohan; Shrine, Nick; Artigas, María Soler; Wain, Louise V; Hall, Ian P; Jackson, Victoria E; Wyss, Annah B; London, Stephanie J; North, Kari E; Franceschini, Nora; Strachan, David P; Beaty, Terri H; Hokanson, John E; Crapo, James D; Castaldi, Peter J; Chase, Robert P; Bartz, Traci M; Heckbert, Susan R; Psaty, Bruce M; Gharib, Sina A; Zanen, Pieter; Lammers, Jan W; Oudkerk, Matthijs; Groen, H J; Locantore, Nicholas; Tal-Singer, Ruth; Rennard, Stephen I; Vestbo, Jørgen; Timens, Wim; Paré, Peter D; Latourelle, Jeanne C; Dupuis, Josée; O'Connor, George T; Wilk, Jemma B; Kim, Woo Jin; Lee, Mi Kyeong; Oh, Yeon-Mok; Vonk, Judith M; de Koning, Harry J; Leng, Shuguang; Belinsky, Steven A; Tesfaigzi, Yohannes; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Barr, R Graham; Sparrow, David; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lahousse, Lies; Brusselle, Guy G; Stricker, Bruno H; Uitterlinden, André G; Ampleford, Elizabeth J; Bleecker, Eugene R; Woodruff, Prescott G; Meyers, Deborah A; Qiao, Dandi; Lomas, David A; Yim, Jae-Joon; Kim, Deog Kyeom; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Hardin, Megan; Fingerlin, Tasha E; Schwartz, David A; Postma, Dirkje S; MacNee, William; Tobin, Martin D; Silverman, Edwin K; Boezen, H Marike; Cho, Michael H

2017-03-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10 -6 ) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

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

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.

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

PubMed

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

2017-02-01

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

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.

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.

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

Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

PubMed

Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

2016-07-01

Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Geographic Patterns of Genetic Variation in a Broadly Distributed Marine Vertebrate: New Insights into Loggerhead Turtle Stock Structure from Expanded Mitochondrial DNA Sequences

PubMed Central

Shamblin, Brian M.; Bolten, Alan B.; Abreu-Grobois, F. Alberto; Bjorndal, Karen A.; Cardona, Luis; Carreras, Carlos; Clusa, Marcel; Monzón-Argüello, Catalina; Nairn, Campbell J.; Nielsen, Janne T.; Nel, Ronel; Soares, Luciano S.; Stewart, Kelly R.; Vilaça, Sibelle T.; Türkozan, Oguz; Yilmaz, Can; Dutton, Peter H.

2014-01-01

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (∼800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology. PMID:24465810

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.

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.

A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

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

Bradshaw, Niels; Levdikov, Vladimir M.; Zimanyi, Christina M.

PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activitymore » in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site.« less

Co-segregation of social cognition, executive function and local processing style in children with ASD, their siblings and normal controls.

PubMed

Oerlemans, Anoek M; Droste, Katharina; van Steijn, Daphne J; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2013-12-01

Cognitive research proposes that social cognition (SC), executive functions (EF) and local processing style (weak CC) may be fruitful areas for research into the familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The performance of 140 children with ASD, 172 siblings and 127 controls on tasks measuring SC (face recognition, affective prosody, and facial emotion recognition), EF (inhibition, cognitive flexibility, and verbal working memory) and local processing style was assessed. Compelling evidence was found for the interrelatedness of SC and EF, but not local processing style, within individuals and within families, suggesting that these domains tend to co-segregate in ASD. Using the underlying shared variance of these constructs in genetic research may increase the power for detecting susceptibility genes for ASD.

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.

Exploring the Relationship Between Autistic-Like Traits and ADHD Behaviors in Early Childhood: Findings from a Community Twin Study of 2-Year-Olds

PubMed Central

Ronald, Angelica; Edelson, Lisa R.; Asherson, Philip; Saudino, Kimberly J.

2014-01-01

Behaviors characteristic of autism and ADHD emerge in early childhood, yet research investigating their comorbidity has focused on older children. This study aimed to explore the nature of the relationship between autistic-like traits and ADHD behaviors in a community sample of 2-year-olds. Twins from the Boston University Twin Project (N=312 pairs) were assessed by their parents on autistic-like traits and ADHD behaviors using the Childhood Behavior Checklist. Phenotypic analyses showed that after controlling for general cognitive ability and socioeconomic status, autistic-like traits (total scale as well as social and nonsocial subscales) correlated positively with ADHD behaviors (r=0.23–0.26). Structural equation model-fitting analyses revealed that there were modest shared genetic influences between ADHD- and autistic traits (genetic correlation = 0.27) as well as some common environmental influences explaining their covariation. Implications for identifying shared biological pathways underlying autistic-like traits and ADHD behaviors are discussed. PMID:19908138

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.

Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1

PubMed Central

Capellini, Terence D.; Vaccari, Giulia; Ferretti, Elisabetta; Fantini, Sebastian; He, Mu; Pellegrini, Massimo; Quintana, Laura; Di Giacomo, Giuseppina; Sharpe, James; Selleri, Licia; Zappavigna, Vincenzo

2010-01-01

The genetic pathways underlying shoulder blade development are largely unknown, as gene networks controlling limb morphogenesis have limited influence on scapula formation. Analysis of mouse mutants for Pbx and Emx2 genes has suggested their potential roles in girdle development. In this study, by generating compound mutant mice, we examined the genetic control of scapula development by Pbx genes and their functional relationship with Emx2. Analyses of Pbx and Pbx1;Emx2 compound mutants revealed that Pbx genes share overlapping functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process. Here, we provide a biochemical basis for Pbx1;Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterodimers. Moreover, the expression of genes crucial for scapula development is altered in these mutants, indicating that Pbx genes act upstream of essential pathways for scapula formation. In particular, expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants. We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate its transcription via this potential regulatory element. Our results establish an essential role for Pbx1 in genetic interactions with its family members and with Emx2 and delineate novel regulatory networks in shoulder girdle development. PMID:20627960

Corporate control and global governance of marine genetic resources

PubMed Central

Österblom, Henrik

2018-01-01

Who owns ocean biodiversity? This is an increasingly relevant question, given the legal uncertainties associated with the use of genetic resources from areas beyond national jurisdiction, which cover half of the Earth’s surface. We accessed 38 million records of genetic sequences associated with patents and created a database of 12,998 sequences extracted from 862 marine species. We identified >1600 sequences from 91 species associated with deep-sea and hydrothermal vent systems, reflecting commercial interest in organisms from remote ocean areas, as well as a capacity to collect and use the genes of such species. A single corporation registered 47% of all marine sequences included in gene patents, exceeding the combined share of 220 other companies (37%). Universities and their commercialization partners registered 12%. Actors located or headquartered in 10 countries registered 98% of all patent sequences, and 165 countries were unrepresented. Our findings highlight the importance of inclusive participation by all states in international negotiations and the urgency of clarifying the legal regime around access and benefit sharing of marine genetic resources. We identify a need for greater transparency regarding species provenance, transfer of patent ownership, and activities of corporations with a disproportionate influence over the patenting of marine biodiversity. We suggest that identifying these key actors is a critical step toward encouraging innovation, fostering greater equity, and promoting better ocean stewardship. PMID:29881777

The Genetic Basis of Inbreeding Avoidance in House Mice

PubMed Central

Sherborne, Amy L.; Thom, Michael D.; Paterson, Steve; Jury, Francine; Ollier, William E.R.; Stockley, Paula; Beynon, Robert J.; Hurst, Jane L.

2007-01-01

Summary Animals might be able to use highly polymorphic genetic markers to recognize very close relatives and avoid inbreeding [1, 2]. The major histocompatibility complex (MHC) is thought to provide such a marker [1, 3–6] because it influences individual scent in a broad range of vertebrates [6–10]. However, direct evidence is very limited [1, 6, 10, 11]. In house mice (Mus musculus domesticus), the major urinary protein (MUP) gene cluster provides another highly polymorphic scent signal of genetic identity [8, 12–15] that could underlie kin recognition. We demonstrate that wild mice breeding freely in seminatural enclosures show no avoidance of mates with the same MHC genotype when genome-wide similarity is controlled. Instead, inbreeding avoidance is fully explained by a strong deficit in successful matings between mice sharing both MUP haplotypes. Single haplotype sharing is not a good guide to the identification of full sibs, and there was no evidence of behavioral imprinting on maternal MHC or MUP haplotypes. This study, the first to examine wild animals with normal variation in MHC, MUP, and genetic background, demonstrates that mice use self-referent matching of a species-specific [16, 17] polymorphic signal to avoid inbreeding. Recognition of close kin as unsuitable mates might be more variable across species than a generic vertebrate-wide ability to avoid inbreeding based on MHC. PMID:17997307

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.

A Children of Twins Study of parental divorce and offspring psychopathology.

PubMed

D'Onofrio, Brian M; Turkheimer, Eric; Emery, Robert E; Maes, Hermine H; Silberg, Judy; Eaves, Lindon J

2007-07-01

Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed.

Multivariate Analysis of the Cotton Seed Ionome Reveals a Shared Genetic Architecture

PubMed Central

Pauli, Duke; Ziegler, Greg; Ren, Min; Jenks, Matthew A.; Hunsaker, Douglas J.; Zhang, Min; Baxter, Ivan; Gore, Michael A.

2018-01-01

To mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutum L.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions. PMID:29437829

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.

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 ...

Genetic and molecular bases of yield-associated traits: a translational biology approach between rice and wheat.

PubMed

Valluru, Ravi; Reynolds, Matthew P; Salse, Jerome

2014-07-01

Transferring the knowledge bases between related species may assist in enlarging the yield potential of crop plants. Being cereals, rice and wheat share a high level of gene conservation; however, they differ at metabolic levels as a part of the environmental adaptation resulting in different yield capacities. This review focuses on the current understanding of genetic and molecular regulation of yield-associated traits in both crop species, highlights the similarities and differences and presents the putative knowledge gaps. We focus on the traits associated with phenology, photosynthesis, and assimilate partitioning and lodging resistance; the most important drivers of yield potential. Currently, there are large knowledge gaps in the genetic and molecular control of such major biological processes that can be filled in a translational biology approach in transferring genomics and genetics informations between rice and wheat.

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.

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.

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.

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.

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

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

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 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.

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

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.

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.

Joint analysis of binary and quantitative traits with data sharing and outcome-dependent sampling.

PubMed

Zheng, Gang; Wu, Colin O; Kwak, Minjung; Jiang, Wenhua; Joo, Jungnam; Lima, Joao A C

2012-04-01

We study the analysis of a joint association between a genetic marker with both binary (case-control) and quantitative (continuous) traits, where the quantitative trait values are only available for the cases due to data sharing and outcome-dependent sampling. Data sharing becomes common in genetic association studies, and the outcome-dependent sampling is the consequence of data sharing, under which a phenotype of interest is not measured for some subgroup. The trend test (or Pearson's test) and F-test are often, respectively, used to analyze the binary and quantitative traits. Because of the outcome-dependent sampling, the usual F-test can be applied using the subgroup with the observed quantitative traits. We propose a modified F-test by also incorporating the genotype frequencies of the subgroup whose traits are not observed. Further, a combination of this modified F-test and Pearson's test is proposed by Fisher's combination of their P-values as a joint analysis. Because of the correlation of the two analyses, we propose to use a Gamma (scaled chi-squared) distribution to fit the asymptotic null distribution for the joint analysis. The proposed modified F-test and the joint analysis can also be applied to test single trait association (either binary or quantitative trait). Through simulations, we identify the situations under which the proposed tests are more powerful than the existing ones. Application to a real dataset of rheumatoid arthritis is presented. © 2012 Wiley Periodicals, Inc.

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.

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.

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

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

Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population.

PubMed

Aiba, Yoshihiro; Yamazaki, Keiko; Nishida, Nao; Kawashima, Minae; Hitomi, Yuki; Nakamura, Hitomi; Komori, Atsumasa; Fuyuno, Yuta; Takahashi, Atsushi; Kawaguchi, Takaaki; Takazoe, Masakazu; Suzuki, Yasuo; Motoya, Satoshi; Matsui, Toshiyuki; Esaki, Motohiro; Matsumoto, Takayuki; Kubo, Michiaki; Tokunaga, Katsushi; Nakamura, Minoru

2015-09-01

We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10(-2) and P=8.40 × 10(-3), respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10(-2), P=3.88 × 10(-2) and P=2.04 × 10(-2), respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: an introduction to this Special Issue of Schizophrenia Research.

PubMed

Swerdlow, Neal R; Gur, Raquel E; Braff, David L

2015-04-01

The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case-control ascertainment strategy (COGS-2) (cumulative "n">4000). COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case-control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case-control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case-control design facilitated the accrual of a larger "n", permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. Published by Elsevier B.V.

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: An introduction to this Special Issue of schizophrenia research

PubMed Central

Swerdlow, Neal R.; Gur, Raquel E.; Braff, David L.

2014-01-01

Background The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Methods Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case–control ascertainment strategy (COGS-2) (cumulative “n” > 4000). Results COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case–control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case–control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case–control design facilitated the accrual of a larger “n”, permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. Discussion The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. PMID:25454799

Cognitive content specificity in anxiety and depressive disorder symptoms: a twin study of cross-sectional associations with anxiety sensitivity dimensions across development.

PubMed

Brown, H M; Waszczuk, M A; Zavos, H M S; Trzaskowski, M; Gregory, A M; Eley, T C

2014-12-01

The classification of anxiety and depressive disorders has long been debated and has important clinical implications. The present study combined a genetically sensitive design and multiple time points to investigate cognitive content specificity in anxiety and depressive disorder symptoms across anxiety sensitivity dimensions, a cognitive distortion implicated in both disorders. Phenotypic and genetic correlations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were examined at five waves of data collection within childhood, adolescence and early adulthood in two representative twin studies (n pairs = 300 and 1372). The physical concerns dimension of anxiety sensitivity (fear of bodily symptoms) was significantly associated with anxiety but not depression at all waves. Genetic influences on physical concerns overlapped substantially more with anxiety than depression. Conversely, mental concerns (worry regarding cognitive control) were phenotypically more strongly associated with depression than anxiety. Social concerns (fear of publicly observable symptoms of anxiety) were associated with both anxiety and depression in adolescence. Genetic influences on mental and social concerns were shared to a similar extent with both anxiety and depression. Phenotypic patterns of cognitive specificity and broader genetic associations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were similar at all waves. Both disorder-specific and shared cognitive concerns were identified, suggesting it is appropriate to classify anxiety and depression as distinct but related disorders and confirming the clinical perspective that cognitive therapy is most likely to benefit by targeting cognitive concerns relating specifically to the individual's presenting symptoms across development.

Attentional switching forms a genetic link between attention problems and autistic traits in adults.

PubMed

Polderman, T J C; Hoekstra, R A; Vinkhuyzen, A A E; Sullivan, P F; van der Sluis, S; Posthuma, D

2013-09-01

Attention deficit hyperactivity disorder (ADHD) symptoms and autistic traits often occur together. The pattern and etiology of co-occurrence are largely unknown, particularly in adults. This study investigated the co-occurrence between both traits in detail, and subsequently examined the etiology of the co-occurrence, using two independent adult population samples. Method Data on ADHD traits (Inattention and Hyperactivity/Impulsivity) were collected in a population sample (S1, n = 559) of unrelated individuals. Data on Attention Problems (AP) were collected in a population-based family sample of twins and siblings (S2, n = 560). In both samples five dimensions of autistic traits were assessed (social skills, routine, attentional switching, imagination, patterns). Hyperactive traits (S1) did not correlate substantially with the autistic trait dimensions. For Inattention (S1) and AP (S2), the correlations with the autistic trait dimensions were low, apart from a prominent correlation with the attentional switching scale (0.47 and 0.32 respectively). Analyses in the genetically informative S2 revealed that this association could be explained by a shared genetic factor. Our findings suggest that the co-occurrence of ADHD traits and autistic traits in adults is not determined by problems with hyperactivity, social skills, imagination or routine preferences. Instead, the association between those traits is due primarily to shared attention-related problems (inattention and attentional switching capacity). As the etiology of this association is purely genetic, biological pathways involving attentional control could be a promising focus of future studies aimed at unraveling the genetic causes of these disorders.

Shared and unique common genetic determinants between pediatric and adult celiac disease.

PubMed

Senapati, Sabyasachi; Sood, Ajit; Midha, Vandana; Sood, Neena; Sharma, Suresh; Kumar, Lalit; Thelma, B K

2016-07-22

Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done. The database included basic demographic characteristics, clinical presentations, associated diseases and complications, if any. The genotype dataset was acquired for children (n = 217) and adult CD patients (n = 340) and controls (n = 736) using Immunochip. Association analysis was performed using logistic regression model to identify susceptibility genetic variants. The predominant form of CD was classical CD in both pediatric and adult CD groups. There was remarkable similarity between pediatric and adult CD except for quantitative differences between the two groups such as female preponderance, non-classical presentation, co-occurrence of other autoimmune diseases being more common amongst adult CD. Notably, same HLA-DQ2 and -DQ8 haplotypes were established as the major risk factors in both types of CD. In addition, a few suggestively associated (p < 5 × 10(-4)) non-HLA markers were identified of which only ANK3 (rs4948256-A; rs10994257-T) was found to be shared and explain risk for ~45 % of CD patients with HLA allele. Overall phenotypic similarity between pediatric and adult CD groups can be explained by contribution of same HLA risk alleles. Different non-HLA genes/loci with minor risk seem to play crucial role in disease onset and extra intestinal manifestation of CD. None of the non-HLA risk variants reached genome-wide significance, however most of them were shown to have functional implication to disease pathogenesis. Functional relevance of our findings needs to be investigated to address clinical heterogeneity of CD. This present study is the first comparative study based on common genetic markers to suggest that CD in pediatric age group and in adults are the spectrum of the same disease with novel and shared genetic risk determinants. Follow-up fine mapping studies with larger study cohorts are warranted for further genetic investigation.

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

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

[Genetic variability of the Bemisia tabaci (Gennadius) biotype B (Hemiptera: Aleyrodidae) in vegetable crops in São Luís, state of Maranhão, Brazil].

PubMed

Da Silva, Maria C; De Lemos, Raimunda N S; Lima, Luzia H C; Gourlart Filho, Luiz R; Pereira, Silma R F

2009-01-01

The RAPD technique is widely used to investigate the distinct genetic characteristics of the complex Bemisia tabaci (Gennadius), which is currently constituted of approximately 41 biotypes. The objective of this research was to characterize populations of whitefly collected in crops of agricultural producing areas in São Luís, MA, like okra, beans and pepper, using RAPD molecular markers. Females from nine whitefly populations were analyzed and compared with B. tabaci biotype B taken from poinsettia culture of Embrapa Genetic Resources and Biotechnology (Brasília, DF). Twelve out of the 20 primers tested produced specific band patterns suitable to confirm that the evaluated specimens belong to the biotype B of B. tabaci, despite the high percentage of detected polymorphism. The analysis of the 96 RAPD molecular markers generated indicated that the populations on okra, beans and pepper were grouped according to the host cultures, sharing 80, 76 and 45% of genetic similarity, respectively, when compared with the control population of B. tabaci biotype B. A lower selective pressure was observed with the population of whitefly collected on pepper and minor genetic variability in the whitefly populations collected on okra and bean, when compared with the control population.

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…

[Gigantism: a mystery explained].

PubMed

Beckers, Alb

2002-01-01

Acromegaly was first described by Pierre Marie in 1886. Some years later, it became clear that acromegaly and gigantism share the same etiology: GH hypersecretion due to a pituitary adenoma, induces gigantism if already present during puberty, or an acromegalic if it appears only during the adulthood. During the XXth century, the disease has been well described and is now well controlled with several treatments. Recently, genetic alterations responsible for the disease have been elucidated.

Genetic population structure in the yellow mongoose, Cynictis penicillata.

PubMed

Van Vuuren, B J; Robinson, T J

1997-12-01

Phylogeographic structure was determined for the yellow mongoose, Cynictis penicillata, using mtDNA RFLPs and control region sequences. The RFLP analysis revealed 13 haplotypes which showed weak geographical patterning consistent with a recent range expansion from a refugial population(s). An analysis of molecular variance (AMOVA) revealed no correspondence between mtDNA phylogeography and subspecies delimitation, nor between matrilines and areas characterized by a high incidence of the viverrid-type rabies, of which the yellow mongoose is the principal vector. The lack of structure was also shown by control region sequences although four of the maternal lineages shared a near-perfect 81 bp repeat. We speculate that regional hot spots of the viverrid rabies biotype reflect population density differences in the yellow mongoose that are not underscored by genetic partitioning, at least at the level of resolution provided by our analyses.

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.

Autism Spectrum Disorder (ASD) and Fragile X Syndrome (FXS): Two Overlapping Disorders Reviewed through Electroencephalography—What Can be Interpreted from the Available Information?

PubMed Central

Mc Devitt, Niamh; Gallagher, Louise; Reilly, Richard B.

2015-01-01

Autism Spectrum Disorder (ASD) and Fragile X syndrome (FXS) are neurodevelopmental disorders with different but potentially related neurobiological underpinnings, which exhibit significant overlap in their behavioural symptoms. FXS is a neurogenetic disorder of known cause whereas ASD is a complex genetic disorder, with both rare and common genetic risk factors and likely genetic and environmental interaction effects. A comparison of the phenotypic presentation of the two disorders may highlight those symptoms that are more likely to be under direct genetic control, for example in FXS as opposed to shared symptoms that are likely to be under the control of multiple mechanisms. This review is focused on the application and analysis of electroencephalography data (EEG) in ASD and FXS. Specifically, Event Related Potentials (ERP) and resting state studies (rEEG) studies investigating ASD and FXS cohorts are compared. This review explores the electrophysiological similarities and differences between the two disorders in addition to the potentially associated neurobiological mechanisms at play. A series of pertinent research questions which are suggested in the literature are also posed within the review. PMID:25826237

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

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

Social network community structure and the contact-mediated sharing of commensal E. coli among captive rhesus macaques (Macaca mulatta).

PubMed

Balasubramaniam, Krishna; Beisner, Brianne; Guan, Jiahui; Vandeleest, Jessica; Fushing, Hsieh; Atwill, Edward; McCowan, Brenda

2018-01-01

In group-living animals, heterogeneity in individuals' social connections may mediate the sharing of microbial infectious agents. In this regard, the genetic relatedness of individuals' commensal gut bacterium Escherichia coli may be ideal to assess the potential for pathogen transmission through animal social networks. Here we use microbial phylogenetics and population genetics approaches, as well as host social network reconstruction, to assess evidence for the contact-mediated sharing of E. coli among three groups of captively housed rhesus macaques ( Macaca mulatta ), at multiple organizational scales. For each group, behavioral data on grooming, huddling, and aggressive interactions collected for a six-week period were used to reconstruct social network communities via the Data Cloud Geometry (DCG) clustering algorithm. Further, an E. coli isolate was biochemically confirmed and genotypically fingerprinted from fecal swabs collected from each macaque. Population genetics approaches revealed that Group Membership, in comparison to intrinsic attributes like age, sex, and/or matriline membership of individuals, accounted for the highest proportion of variance in E. coli genotypic similarity. Social network approaches revealed that such sharing was evident at the community-level rather than the dyadic level. Specifically, although we found no links between dyadic E. coli similarity and social contact frequencies, similarity was significantly greater among macaques within the same social network communities compared to those across different communities. Moreover, tests for one of our study-groups confirmed that E. coli isolated from macaque rectal swabs were more genotypically similar to each other than they were to isolates from environmentally deposited feces. In summary, our results suggest that among frequently interacting, spatially constrained macaques with complex social relationships, microbial sharing via fecal-oral, social contact-mediated routes may depend on both individuals' direct connections and on secondary network pathways that define community structure. They lend support to the hypothesis that social network communities may act as bottlenecks to contain the spread of infectious agents, thereby encouraging disease control strategies to focus on multiple organizational scales. Future directions includeincreasing microbial sampling effort per individual to better-detect dyadic transmission events, and assessments of the co-evolutionary links between sociality, infectious agent risk, and host immune function.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

PubMed

St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G

2018-02-01

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

A Children of Twins Study of parental divorce and offspring psychopathology

PubMed Central

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Maes, Hermine H.; Silberg, Judy; Eaves, Lindon J.

2010-01-01

Background Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. Method We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. Results The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. Conclusions The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed. PMID:17593147

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 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.

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.

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.

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

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

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

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

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.

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

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

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.

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

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.

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.

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

A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

PubMed Central

Bradshaw, Niels; Levdikov, Vladimir M; Zimanyi, Christina M; Gaudet, Rachelle; Wilkinson, Anthony J; Losick, Richard

2017-01-01

PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activity in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site. DOI: http://dx.doi.org/10.7554/eLife.26111.001 PMID:28527238

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

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

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

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.

Nuclear, chloroplast, and mitochondrial data of a US cannabis DNA database.

PubMed

Houston, Rachel; Birck, Matthew; LaRue, Bobby; Hughes-Stamm, Sheree; Gangitano, David

2018-05-01

As Cannabis sativa (marijuana) is a controlled substance in many parts of the world, the ability to track biogeographical origin of cannabis could provide law enforcement with investigative leads regarding its trade and distribution. Population substructure and inbreeding may cause cannabis plants to become more genetically related. This genetic relatedness can be helpful for intelligence purposes. Analysis of autosomal, chloroplast, and mitochondrial DNA allows for not only prediction of biogeographical origin of a plant but also discrimination between individual plants. A previously validated, 13-autosomal STR multiplex was used to genotype 510 samples. Samples were analyzed from four different sites: 21 seizures at the US-Mexico border, Northeastern Brazil, hemp seeds purchased in the US, and the Araucania area of Chile. In addition, a previously reported multi-loci system was modified and optimized to genotype five chloroplast and two mitochondrial markers. For this purpose, two methods were designed: a homopolymeric STR pentaplex and a SNP triplex with one chloroplast (Cscp001) marker shared by both methods for quality control. For successful mitochondrial and chloroplast typing, a novel real-time PCR quantitation method was developed and validated to accurately estimate the quantity of the chloroplast DNA (cpDNA) using a synthetic DNA standard. Moreover, a sequenced allelic ladder was also designed for accurate genotyping of the homopolymeric STR pentaplex. For autosomal typing, 356 unique profiles were generated from the 425 samples that yielded full STR profiles and 25 identical genotypes within seizures were observed. Phylogenetic analysis and case-to-case pairwise comparisons of 21 seizures at the US-Mexico border, using the Fixation Index (F ST ) as genetic distance, revealed the genetic association of nine seizures that formed a reference population. For mitochondrial and chloroplast typing, subsampling was performed, and 134 samples were genotyped. Complete haplotypes (STRs and SNPs) were observed for 127 samples. As expected, extensive haplotype sharing was observed; five distinguishable haplotypes were detected. In the reference population, the same haplotype was observed 39 times and two unique haplotypes were also detected. Haplotype sharing was observed between the US border seizures, Brazil, and Chile, while the hemp samples generated a distinct haplotype. Phylogenetic analysis of the four populations was performed, and results revealed that both autosomal and lineage markers could discern population substructure.

Neural sex modifies the function of a C. elegans sensory circuit.

PubMed

Lee, Kyunghwa; Portman, Douglas S

2007-11-06

Though sex differences in animal behavior are ubiquitous, their neural and genetic underpinnings remain poorly understood. In particular, the role of functional differences in the neural circuitry that is shared by both sexes has not been extensively investigated. We have addressed these issues with C. elegans olfaction, a simple innate behavior mediated by sexually isomorphic neurons. Though males respond to the same olfactory attractants as do hermaphrodites, we find that each sex has a characteristic repertoire of olfactory preferences. These are not secondary to other sex-specific behaviors and do not require signaling from the gonad. Sex-specific olfactory preferences are controlled by tra-1, the master regulator of C. elegans sexual differentiation. Moreover, the genetic masculinization of neurons in an otherwise wild-type hermaphrodite is sufficient to switch the sexual phenotype of olfactory preference behavior. These studies reveal novel and unexpected sex differences in a C. elegans sensory behavior that is exhibited by both sexes. Our results indicate that these differences are a function of the chromosomally determined sexual identity of shared neural circuitry.

Unfit for work: Health and labour-market prospects.

PubMed

Böckerman, Petri; Maczulskij, Terhi

2018-02-01

The aim of this study was to examine whether health status (number of chronic diseases, health shock and use of tranquilizers/sleeping pills) is related to labour-market outcomes later in life. Twin data for Finnish men and women who were at least 33 years old in 1990 were linked to comprehensive register-based information on unemployment and the incidence of disability pension. We used the within-twin dimension of the data to account for shared family and genetic factors. Self-reported information on the number of diagnosed chronic diseases, health shock and drug use were obtained from the 1975 and 1981 twin surveys, when the twins were at least 18 years old. Unemployment months and the incidence of disability pension were measured during prime working age over the 1990-2004/2009 period. Poor health status is significantly positively related to unemployment and the incidence of disability pension. The results are robust to controlling for shared family and genetic factors and the key measures of risky health behaviours (alcohol use, lifetime smoking and body mass index). Health status is a fundamental determinant of long-term labour-market outcomes.

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 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 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.

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.

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.

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.

Addiction Genetics and Pleiotropic Effects of Common Haplotypes that Make Polygenic Contributions to Vulnerability to Substance Dependence

PubMed Central

Uhl, George R.; Drgon, Tomas; Johnson, Catherine; Liu, Qing-Rong

2016-01-01

Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances. Twin data suggest that most of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Molecular genetic studies, especially genomewide and candidate gene association studies, have elucidated common haplotypes in dozens of genes that appear to make polygenic contributions to vulnerability to developing dependence. Most genes that harbor currently identified addiction-associated haplotypes are expressed in the brain. Haplotypes in many of the same genes are identified in genomewide association studies that compare allele frequencies in substance dependent vs. control individuals from European, African, and Asian racial/ethnic backgrounds. Many of these addiction-associated haplotypes display pleiotropic influences on a variety of related brain-based phenotypes that display 1) substantial heritability and 2) clinical cooccurence with substance dependence. PMID:19152208

Virus evolution and transmission in an ever more connected world

PubMed Central

Pybus, Oliver G.; Tatem, Andrew J.; Lemey, Philippe

2015-01-01

The frequency and global impact of infectious disease outbreaks, particularly those caused by emerging viruses, demonstrate the need for a better understanding of how spatial ecology and pathogen evolution jointly shape epidemic dynamics. Advances in computational techniques and the increasing availability of genetic and geospatial data are helping to address this problem, particularly when both information sources are combined. Here, we review research at the intersection of evolutionary biology, human geography and epidemiology that is working towards an integrated view of spatial incidence, host mobility and viral genetic diversity. We first discuss how empirical studies have combined viral spatial and genetic data, focusing particularly on the contribution of evolutionary analyses to epidemiology and disease control. Second, we explore the interplay between virus evolution and global dispersal in more depth for two pathogens: human influenza A virus and chikungunya virus. We discuss the opportunities for future research arising from new analyses of human transportation and trade networks, as well as the associated challenges in accessing and sharing relevant spatial and genetic data. PMID:26702033

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

PubMed

Wray, Naomi R; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M; Abdellaoui, Abdel; Adams, Mark J; Agerbo, Esben; Air, Tracy M; Andlauer, Till M F; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan F T; Bigdeli, Tim B; Binder, Elisabeth B; Blackwood, Douglas R H; Bryois, Julien; Buttenschøn, Henriette N; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan I R; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E; Crowley, Cheynna A; Dashti, Hassan S; Davies, Gail; Deary, Ian J; Degenhardt, Franziska; Derks, Eske M; Direk, Nese; Dolan, Conor V; Dunn, Erin C; Eley, Thalia C; Eriksson, Nicholas; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K; Forstner, Andreas J; Frank, Josef; Gaspar, Héléna A; Gill, Michael; Giusti-Rodríguez, Paola; Goes, Fernando S; Gordon, Scott D; Grove, Jakob; Hall, Lynsey S; Hannon, Eilis; Hansen, Christine Søholm; Hansen, Thomas F; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M; Hu, Ming; Hyde, Craig L; Ising, Marcus; Jansen, Rick; Jin, Fulai; Jorgenson, Eric; Knowles, James A; Kohane, Isaac S; Kraft, Julia; Kretzschmar, Warren W; Krogh, Jesper; Kutalik, Zoltán; Lane, Jacqueline M; Li, Yihan; Li, Yun; Lind, Penelope A; Liu, Xiaoxiao; Lu, Leina; MacIntyre, Donald J; MacKinnon, Dean F; Maier, Robert M; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E; Mehta, Divya; Middeldorp, Christel M; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mill, Jonathan; Mondimore, Francis M; Montgomery, Grant W; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G; Nyholt, Dale R; O'Reilly, Paul F; Oskarsson, Hogni; Owen, Michael J; Painter, Jodie N; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E; Pettersson, Erik; Peyrot, Wouter J; Pistis, Giorgio; Posthuma, Danielle; Purcell, Shaun M; Quiroz, Jorge A; Qvist, Per; Rice, John P; Riley, Brien P; Rivera, Margarita; Saeed Mirza, Saira; Saxena, Richa; Schoevers, Robert; Schulte, Eva C; Shen, Ling; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Sinnamon, Grant B C; Smit, Johannes H; Smith, Daniel J; Stefansson, Hreinn; Steinberg, Stacy; Stockmeier, Craig A; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A; Thorgeirsson, Thorgeir E; Tian, Chao; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M; Viktorin, Alexander; Visscher, Peter M; Wang, Yunpeng; Webb, Bradley T; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Witt, Stephanie H; Wu, Yang; Xi, Hualin S; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T; Berger, Klaus; Boomsma, Dorret I; Cichon, Sven; Dannlowski, Udo; de Geus, E C J; DePaulo, J Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grabe, Hans J; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Kendler, Kenneth S; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S; Lucae, Susanne; Madden, Pamela F A; Magnusson, Patrik K; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Paciga, Sara A; Pedersen, Nancy L; Penninx, Brenda W J H; Perlis, Roy H; Porteous, David J; Potash, James B; Preisig, Martin; Rietschel, Marcella; Schaefer, Catherine; Schulze, Thomas G; Smoller, Jordan W; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M; Werge, Thomas; Winslow, Ashley R; Lewis, Cathryn M; Levinson, Douglas F; Breen, Gerome; Børglum, Anders D; Sullivan, Patrick F

2018-05-01

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

A genetically informed study of the association between harsh punishment and offspring behavioral problems.

PubMed

Lynch, Stacy K; Turkheimer, Eric; D'Onofrio, Brian M; Mendle, Jane; Emery, Robert E; Slutske, Wendy S; Martin, Nicholas G

2006-06-01

Conclusions about the effects of harsh parenting on children have been limited by research designs that cannot control for genetic or shared environmental confounds. The present study used a sample of children of twins and a hierarchical linear modeling statistical approach to analyze the consequences of varying levels of punishment while controlling for many confounding influences. The sample of 887 twin pairs and 2,554 children came from the Australian Twin Registry. Although corporal punishment per se did not have significant associations with negative childhood outcomes, harsher forms of physical punishment did appear to have specific and significant effects. The observed association between harsh physical punishment and negative outcomes in children survived a relatively rigorous test of its causal status, thereby increasing the authors' conviction that harsh physical punishment is a serious risk factor for children. ((c) 2006 APA, all rights reserved).

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

Wagner, Maggie R.; Lundberg, Derek S.; del Rio, Tijana G.

Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant's genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots of Boechera stricta (Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome ismore » evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.« less

Memory and modularity in cell-fate decision making

NASA Astrophysics Data System (ADS)

Norman, Thomas M.; Lord, Nathan D.; Paulsson, Johan; Losick, Richard

2013-11-01

Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is `memoryless', exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.

A Genetically Informed Study of the Association Between Harsh Punishment and Offspring Behavioral Problems

PubMed Central

Lynch, Stacy K.; Turkheimer, Eric; D’Onofrio, Brian M.; Mendle, Jane; Emery, Robert E.; Slutske, Wendy S.; Martin, Nicholas G.

2010-01-01

Conclusions about the effects of harsh parenting on children have been limited by research designs that cannot control for genetic or shared environmental confounds. The present study used a sample of children of twins and a hierarchical linear modeling statistical approach to analyze the consequences of varying levels of punishment while controlling for many confounding influences. The sample of 887 twin pairs and 2,554 children came from the Australian Twin Registry. Although corporal punishment per se did not have significant associations with negative childhood outcomes, harsher forms of physical punishment did appear to have specific and significant effects. The observed association between harsh physical punishment and negative outcomes in children survived a relatively rigorous test of its causal status, thereby increasing the authors’ conviction that harsh physical punishment is a serious risk factor for children. PMID:16756394

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.

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.

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

PubMed Central

Hinks, A; Cobb, J; Ainsworth, H C; Marion, M C; Comeau, M E; Sudman, M; Han, B; Becker, M L; Bohnsack, J F; de Bakker, P I W; Haas, J P; Hazen, M; Lovell, D J; Nigrovic, P A; Nordal, E; Punnaro, M; Rosenberg, A M; Rygg, M; Wise, C A; Videm, V; Wedderburn, L R; Yarwood, A; Yeung, R S M; Prahalad, S; Langefeld, C D; Raychaudhuri, S; Thompson, S D; Thomson, W

2017-01-01

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. PMID:27998952

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

PubMed

Hinks, A; Bowes, J; Cobb, J; Ainsworth, H C; Marion, M C; Comeau, M E; Sudman, M; Han, B; Becker, M L; Bohnsack, J F; de Bakker, P I W; Haas, J P; Hazen, M; Lovell, D J; Nigrovic, P A; Nordal, E; Punnaro, M; Rosenberg, A M; Rygg, M; Smith, S L; Wise, C A; Videm, V; Wedderburn, L R; Yarwood, A; Yeung, R S M; Prahalad, S; Langefeld, C D; Raychaudhuri, S; Thompson, S D; Thomson, W

2017-04-01

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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.

Retrospective reports of parental physical affection and parenting style: a study of Finnish twins.

PubMed

Harlaar, Nicole; Santtila, Pekka; Björklund, Johanna; Alanko, Katarina; Jern, Patrick; Varjonen, Markus; von der Pahlen, Bettina; Sandnabba, Kenneth

2008-08-01

Individual differences in parenting behaviors are due, in part, to genetic factors. In the present study, the authors sought to determine whether the degree of genetic influence varied according to the type of parental behavior under consideration. A population-based sample of 2,334 pairs of Finnish twins provided ratings on the physical affection, control, abusiveness, and indifference shown by their father and mother during childhood. Genetic influences, shared environmental influences, and nonshared environmental influences accounted for a small-to-medium proportion (17%-30%), a small-to-large proportion (22%-44%), and a medium-to-large proportion (37%-55%) of the variance in each parenting measure, respectively. There were no significant differences in effect sizes for mothers and fathers or across the 4 types of parental behavior. The genetic results may reflect characteristic styles with which parents respond to genetically influenced behaviors of individuals (gene-environment correlations) or individual perceptions of this relationship (gene-person correlation processes). The findings have implications for intervention and prevention work with families and for interpretation of evidence for interactions between genes and parenting behaviors.

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.

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.

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis

PubMed Central

Hisa, Kaori; Yanagimachi, Masakatsu D.; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

2017-01-01

Objective Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a ‘shared epitope’ (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. Methods JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Results Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5–11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71–23.7 pc = 0.03). Conclusion PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations. PMID:28182665

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

PubMed

Hisa, Kaori; Yanagimachi, Masakatsu D; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

2017-01-01

Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a 'shared epitope' (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03). PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

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.

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.

A possible genetic association with chronic fatigue in primary Sjögren's syndrome: a candidate gene study.

PubMed

Norheim, Katrine Brække; Le Hellard, Stephanie; Nordmark, Gunnel; Harboe, Erna; Gøransson, Lasse; Brun, Johan G; Wahren-Herlenius, Marie; Jonsson, Roland; Omdal, Roald

2014-02-01

Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

PubMed Central

Viatte, Sebastien; Massey, Jonathan; Bowes, John; Duffus, Kate; Eyre, Stephen; Barton, Anne; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew W.; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Tim D.; Valdes, Ana M.; Wallis, Gillian A.; Wilkinson, J. Mark; Zeggini, Eleftheria

2016-01-01

Objective Genetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study. Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA. PMID:26895230

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.

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.

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 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

Balancing the risks and benefits of genomic data sharing: genome research participants' perspectives.

PubMed

Oliver, J M; Slashinski, M J; Wang, T; Kelly, P A; Hilsenbeck, S G; McGuire, A L

2012-01-01

Technological advancements are rapidly propelling the field of genome research forward, while lawmakers attempt to keep apace with the risks these advances bear. Balancing normative concerns of maximizing data utility and protecting human subjects, whose privacy is at risk due to the identifiability of DNA data, are central to policy decisions. Research on genome research participants making real-time data sharing decisions is limited; yet, these perspectives could provide critical information to ongoing deliberations. We conducted a randomized trial of 3 consent types affording varying levels of control over data release decisions. After debriefing participants about the randomization process, we invited them to a follow-up interview to assess their attitudes toward genetic research, privacy and data sharing. Participants were more restrictive in their reported data sharing preferences than in their actual data sharing decisions. They saw both benefits and risks associated with sharing their genomic data, but risks were seen as less concrete or happening in the future, and were largely outweighed by purported benefits. Policymakers must respect that participants' assessment of the risks and benefits of data sharing and their privacy-utility determinations, which are associated with their final data release decisions, vary. In order to advance the ethical conduct of genome research, proposed policy changes should carefully consider these stakeholder perspectives. Copyright © 2011 S. Karger AG, Basel.

Genetic and intermediate phenotypic susceptibility markers of gastric cancer in Hispanic Americans: a case-control study.

PubMed

Sun, Yuhui; Gu, Jian; Ajani, Jaffer A; Chang, David W; Wu, Xifeng; Stroehlein, John R

2014-10-01

Hispanics are the largest nonwhite ethnic group in the US population, and they have higher incidence and mortality rates for gastric cancer (GC) than whites and Asians. Studies have identified several genetic susceptibility loci and intermediate phenotypic biomarkers for GC in whites and Asians. No studies have evaluated genetic susceptibility and intermediate phenotypic biomarkers in Hispanics. In a case-control study of 132 Hispanic patients with GC (cases) and a control group of 125 Hispanics (controls), the authors evaluated the association of 5 single nucleotide polymorphisms (SNPs) that predispose whites and/or Asians to GC and of 2 intermediate phenotypic markers in peripheral blood leukocytes, ie, telomere length and mitochondrial DNA (mtDNA) copy number, with the GC risk. The variant C allele of the reference SNP rs2294008 in the PSCA gene was associated with a significantly reduced risk of GC (per allele-adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.33-0.77; P = .002). Leukocyte mtDNA copy numbers were significantly lower in GC cases (mean ± standard deviation, 0.91 ± 0.28) than in controls (1.29 ± 0.42; P < .001). When individuals were dichotomized into high and low mtDNA copy number groups based on the median mtDNA copy number value in the controls, those who had a low mtDNA copy number had a significantly increased risk of GC (aOR, 11.00; 95% CI, 4.79-25.23; P < .001) compared with those who had a high mtDNA copy number. Telomere length was not associated significantly with the risk of GC (aOR, 1.21; 95% CI, 0.65-2.27; P = .551). Hispanics share certain genetic susceptibility loci and intermediate phenotypic GC biomarkers with whites and Asians and may also have distinct genetic susceptibility factors. © 2014 American Cancer Society.

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.

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.

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.

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…

The population genetics of sporophytic self-incompatibility in three hybridizing senecio (asteraceae) species with contrasting population histories.

PubMed

Brennan, Adrian C; Harris, Stephen A; Hiscock, Simon J

2013-05-01

Hybridization generates evolutionary novelty and spreads adaptive variation. By promoting outcrossing, plant self-incompatibility (SI) systems also favor interspecific hybridization because the S locus is under strong negative frequency-dependent balancing selection. This study investigates the SI mating systems of three hybridizing Senecio species with contrasting population histories. Senecio aethnensis and S. chrysanthemifolius native to Sicily, form a hybrid zone at intermediate altitudes on Mount Etna, and their neo-homoploid hybrid species, S. squalidus, has colonized disturbed urban habitats in the UK during the last 150 years. We show that all three species express sporophytic SI (SSI), where pollen incompatibility is controlled by the diploid parental genome, and that SSI is inherited and functions normally in hybrids. Large-scale crossing studies of wild sampled populations allowed direct comparison of SSI between species and found that the main impacts of colonization in S. squalidus compared to Sicilian Senecio was a reduced number of S alleles, increased S allele frequencies, and increased interpopulation S allele sharing. In general, many S alleles were shared between species and the S locus showed reduced intra- and interspecific population genetic structure compared to molecular genetic markers, indicative of enhanced effective gene flow due to balancing selection. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

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.

Elucidation of the genetic architecture of self-incompatibility in olive: Evolutionary consequences and perspectives for orchard management.

PubMed

Saumitou-Laprade, Pierre; Vernet, Philippe; Vekemans, Xavier; Billiard, Sylvain; Gallina, Sophie; Essalouh, Laila; Mhaïs, Ali; Moukhli, Abdelmajid; El Bakkali, Ahmed; Barcaccia, Gianni; Alagna, Fiammetta; Mariotti, Roberto; Cultrera, Nicolò G M; Pandolfi, Saverio; Rossi, Martina; Khadari, Bouchaïb; Baldoni, Luciana

2017-10-01

The olive ( Olea europaea L.) is a typical important perennial crop species for which the genetic determination and even functionality of self-incompatibility (SI) are still largely unresolved. It is still not known whether SI is under gametophytic or sporophytic genetic control, yet fruit production in orchards depends critically on successful ovule fertilization. We studied the genetic determination of SI in olive in light of recent discoveries in other genera of the Oleaceae family. Using intra- and interspecific stigma tests on 89 genotypes representative of species-wide olive diversity and the compatibility/incompatibility reactions of progeny plants from controlled crosses, we confirmed that O. europaea shares the same homomorphic diallelic self-incompatibility (DSI) system as the one recently identified in Phillyrea angustifolia and Fraxinus ornus . SI is sporophytic in olive. The incompatibility response differs between the two SI groups in terms of how far pollen tubes grow before growth is arrested within stigma tissues. As a consequence of this DSI system, the chance of cross-incompatibility between pairs of varieties in an orchard is high (50%) and fruit production may be limited by the availability of compatible pollen. The discovery of the DSI system in O. europaea will undoubtedly offer opportunities to optimize fruit production.

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.

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.

Factor Structure and Heritability of Endophenotypes in Schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)

PubMed Central

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

2018-01-01

Background Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. Methods The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003–2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Results Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Conclusions Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. PMID:25682549

Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).

PubMed

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

2015-04-01

Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status

PubMed Central

Adib-Samii, Poneh; Rost, Natalia; Traylor, Matthew; Devan, William; Biffi, Alessandro; Lanfranconi, Silvia; Fitzpatrick, Kaitlin; Bevan, Steve; Kanakis, Allison; Valant, Valerie; Gschwendtner, Andreas; Malik, Rainer; Richie, Alexa; Gamble, Dale; Segal, Helen; Parati, Eugenio A.; Ciusani, Emilio; Holliday, Elizabeth G.; Maguire, Jane; Wardlaw, Joanna; Worrall, Bradford; Bis, Joshua; Wiggins, Kerri L.; Longstreth, Will; Kittner, Steve J.; Cheng, Yu-Ching; Mosley, Thomas; Falcone, Guido J.; Furie, Karen L.; Leiva-Salinas, Carlos; Lau, Benison C.; Khan, Muhammed Saleem; Sharma, Pankaj; Fornage, Myriam; Mitchell, Braxton D.; Psaty, Bruce M.; Sudlow, Cathie; Levi, Christopher; Boncoraglio, Giorgio B.; Rothwell, Peter M.; Meschia, James; Dichgans, Martin; Rosand, Jonathan; Markus, Hugh S.

2013-01-01

Background and Purpose Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction. PMID:23674528

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.

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

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.

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.

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.

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.

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.

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

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

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…

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.

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.

Cholesterol oversynthesis markers define familial combined hyperlipidemia versus other genetic hypercholesterolemias independently of body weight.

PubMed

Baila-Rueda, Lucía; Cenarro, Ana; Lamiquiz-Moneo, Itziar; Perez-Calahorra, Sofía; Bea, Ana M; Marco-Benedí, Victoria; Jarauta, Estíbaliz; Mateo-Gallego, Rocío; Civeira, Fernando

2018-03-01

Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and both share a very high cardiovascular risk. In order to better characterize the metabolic abnormalities associated with these primary hypercholesterolemias, we used noncholesterol sterols, as markers of cholesterol metabolism, to determine their potential differences. Hepatic cholesterol synthesis markers (desmosterol and lanosterol) and intestinal cholesterol absorption markers (sitosterol and campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in normolipidemic controls (n=100). FCHL subjects had lower cholesterol absorption and higher cholesterol synthesis than non-FH GH, FH and controls (P<.001). When noncholesterol sterols were adjusted by body mass index (BMI), FCHL subjects had higher cholesterol synthesis than non-FG GH, FH and controls (P<.001). An increase in BMI was accompanied by increased cholesterol synthesis and decreased cholesterol absorption in non-FH GH, FH and controls. However, this association between BMI and cholesterol synthesis was not observed in FCHL. Non-high-density-lipoprotein cholesterol showed a positive correlation with cholesterol synthesis markers similar to that of BMI in non-FH GH, FH and normolipemic controls, but there was no correlation in FCHL. These results suggest that FCHL and non-FH GH have different mechanisms of production. Cholesterol synthesis and absorption are dependent of BMI in non-FH GH, but cholesterol synthesis is increased as a pathogenic mechanism in FCHL independently of age, gender, APOE and BMI. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Identification of a missense variant in LNPEP that confers psoriasis risk.

PubMed

Cheng, Hui; Li, Yang; Zuo, Xian-Bo; Tang, Hua-Yang; Tang, Xian-Fa; Gao, Jin-Ping; Sheng, Yu-Jun; Yin, Xian-Yong; Zhou, Fu-Sheng; Zhang, Chi; Chen, Gang; Zhu, Jun; Pan, Qian; Liang, Bo; Zheng, Xiao-Dong; Li, Pan; Ding, Yan-Tao; Cheng, Fang; Luo, Jing; Chang, Rui-Xue; Pan, Gong-Bu; Fan, Xing; Wang, Zai-Xing; Zhang, An-Ping; Liu, Jian-Jun; Yang, Sen; Sun, Liang-Dan; Zhang, Xue-Jun

2014-02-01

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway.

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.

Social network community structure and the contact-mediated sharing of commensal E. coli among captive rhesus macaques (Macaca mulatta)

PubMed Central

Beisner, Brianne; Guan, Jiahui; Vandeleest, Jessica; Fushing, Hsieh; Atwill, Edward; McCowan, Brenda

2018-01-01

In group-living animals, heterogeneity in individuals’ social connections may mediate the sharing of microbial infectious agents. In this regard, the genetic relatedness of individuals’ commensal gut bacterium Escherichia coli may be ideal to assess the potential for pathogen transmission through animal social networks. Here we use microbial phylogenetics and population genetics approaches, as well as host social network reconstruction, to assess evidence for the contact-mediated sharing of E. coli among three groups of captively housed rhesus macaques (Macaca mulatta), at multiple organizational scales. For each group, behavioral data on grooming, huddling, and aggressive interactions collected for a six-week period were used to reconstruct social network communities via the Data Cloud Geometry (DCG) clustering algorithm. Further, an E. coli isolate was biochemically confirmed and genotypically fingerprinted from fecal swabs collected from each macaque. Population genetics approaches revealed that Group Membership, in comparison to intrinsic attributes like age, sex, and/or matriline membership of individuals, accounted for the highest proportion of variance in E. coli genotypic similarity. Social network approaches revealed that such sharing was evident at the community-level rather than the dyadic level. Specifically, although we found no links between dyadic E. coli similarity and social contact frequencies, similarity was significantly greater among macaques within the same social network communities compared to those across different communities. Moreover, tests for one of our study-groups confirmed that E. coli isolated from macaque rectal swabs were more genotypically similar to each other than they were to isolates from environmentally deposited feces. In summary, our results suggest that among frequently interacting, spatially constrained macaques with complex social relationships, microbial sharing via fecal-oral, social contact-mediated routes may depend on both individuals’ direct connections and on secondary network pathways that define community structure. They lend support to the hypothesis that social network communities may act as bottlenecks to contain the spread of infectious agents, thereby encouraging disease control strategies to focus on multiple organizational scales. Future directions includeincreasing microbial sampling effort per individual to better-detect dyadic transmission events, and assessments of the co-evolutionary links between sociality, infectious agent risk, and host immune function. PMID:29372120

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 ...

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.

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

PubMed

Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe

2017-05-01

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.

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

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…

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…

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…

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.

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.

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.

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.

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 ...

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

Participants' recall and understanding of genomic research and large-scale data sharing.

PubMed

Robinson, Jill Oliver; Slashinski, Melody J; Wang, Tao; Hilsenbeck, Susan G; McGuire, Amy L

2013-10-01

As genomic researchers are urged to openly share generated sequence data with other researchers, it is important to examine the utility of informed consent documents and processes, particularly as these relate to participants' engagement with and recall of the information presented to them, their objective or subjective understanding of the key elements of genomic research (e.g., data sharing), as well as how these factors influence or mediate the decisions they make. We conducted a randomized trial of three experimental informed consent documents (ICDs) with participants (n = 229) being recruited to genomic research studies; each document afforded varying control over breadth of release of genetic information. Recall and understanding, their impact on data sharing decisions, and comfort in decision making were assessed in a follow-up structured interview. Over 25% did not remember signing an ICD to participate in a genomic study, and the majority (54%) could not correctly identify with whom they had agreed to share their genomic data. However, participants felt that they understood enough to make an informed decision, and lack of recall did not impact final data sharing decisions or satisfaction with participation. These findings raise questions about the types of information participants need in order to provide valid informed consent, and whether subjective understanding and comfort with decision making are sufficient to satisfy the ethical principle of respect for persons.

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.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

PubMed Central

Gu, Tongjun; Gatti, Daniel M.; Srivastava, Anuj; Snyder, Elizabeth M.; Raghupathy, Narayanan; Simecek, Petr; Svenson, Karen L.; Dotu, Ivan; Chuang, Jeffrey H.; Keller, Mark P.; Attie, Alan D.; Braun, Robert E.; Churchill, Gary A.

2016-01-01

RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing. PMID:26614740

Significant genetic differentiation between native and introduced silver carp (Hypophthalmichthys molitrix) inferred from mtDNA analysis

USGS Publications Warehouse

Li, S.-F.; Xu, J.-W.; Yang, Q.-L.; Wang, C.H.; Chapman, D.C.; Lu, G.

2011-01-01

Silver carp Hypophthalmichthys molitrix (Cyprinidae) is native to China and has been introduced to over 80 countries. The extent of genetic diversity in introduced silver carp and the genetic divergence between introduced and native populations remain largely unknown. In this study, 241 silver carp sampled from three major native rivers and two non-native rivers (Mississippi River and Danube River) were analyzed using nucleotide sequences of mitochondrial COI gene and D-loop region. A total of 73 haplotypes were observed, with no haplotype found common to all the five populations and eight haplotypes shared by two to four populations. As compared with introduced populations, all native populations possess both higher haplotype diversity and higher nucleotide diversity, presumably a result of the founder effect. Significant genetic differentiation was revealed between native and introduced populations as well as among five sampled populations, suggesting strong selection pressures might have occurred in introduced populations. Collectively, this study not only provides baseline information for sustainable use of silver carp in their native country (i.e., China), but also offers first-hand genetic data for the control of silver carp in countries (e.g., the United States) where they are considered invasive.

Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

PubMed

Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong

2016-04-01

Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye  = 0.015) and rs4512342 (Pallele  = 0.03, Pgenotye  = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye  = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. © 2016 Wiley Periodicals, Inc.

[Neurobiology of addictive behavior].

PubMed

Ivlieva, N Iu

2011-01-01

Addictive behavior developes after repeated substance use and it typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to the drug use than to other activities. Relapse, the resumption of drug taking after periods of abstinence, remains the major problem for the treatment of addiction. The process of drug addiction shares striking commonalities with neural plasticity associated with natural reward learning and memory and is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. The switch from controlled to compulsive drug seeking represents a transition at the neural level from prefrontal cortical to striatal control. Current neurophysiologic evidence suggests that the development of addiction is to some extent due to neurochemical stimulation of the midbrain dopaminergic system that is traditionally considered as a 'common neural currency' for rewards of most kinds. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity. Environmental factors are crucial in addiction vulnerability and resistese too.

Netting Novel Regulators of Hematopoiesis and Hematologic Malignancies in Zebrafish.

PubMed

Kwan, Wanda; North, Trista E

2017-01-01

Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis. Significantly, perturbations in many of the key developmental signals controlling hematopoiesis are associated with hematological disorders and disease, including anemia, bone marrow failure syndromes, and leukemia. Thus, understanding the regulatory pathways controlling HSPC production and function has important clinical implications. In this review, we describe how the blood system forms and is maintained in zebrafish, with particular focus on new insights into vertebrate hematological regulation gained using this model. The interplay of factors controlling development and disease in the hematopoietic system combined with the unique attributes of the zebrafish make this a powerful platform to discover novel targets for the treatment of hematological disease. © 2017 Elsevier Inc. All rights reserved.

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...

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

Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants

PubMed Central

Menon, Ramkumar; Pearce, Brad; Velez, Digna R; Merialdi, Mario; Williams, Scott M; Fortunato, Stephen J; Thorsen, Poul

2009-01-01

Objective To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. Methods A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined. Results From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants. Conclusion Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians PMID:19527514

Diabetes mellitus in genetically isolated populations in Jordan: prevalence, awareness, glycemic control, and associated factors.

PubMed

Dajani, Rana; Khader, Yousef S; Fatahallah, Raja; El-Khateeb, Mohammad; Shiyab, Abel Halim; Hakooz, Nancy

2012-01-01

Diabetes mellitus is one of the most common non-communicable diseases globally. This study seeks to estimate the prevalence of impaired fasting glycemia and type 2 diabetes mellitus in genetically isolated populations in Jordan: the Circassians and Chechans. Data were analyzed from a cross-sectional study that included a random sample of adult Circassians and Chechans. A subject was defined as affected by diabetes mellitus if diagnosis was known to patient or, according to the American Diabetes Association definition. Impaired fasting glucose was defined as a fasting serum glucose level of ≥6.1 mmol/L (100 mg/dl) but <7 mmol/L. HbA(1c) >7% was defined as 'unsatisfactory' metabolic control. The prevalence of impaired fasting glycemia was 18.5% for Circassians and 14.6% for Chechans. Prevalence of diabetes was 9.6% for Circassians and 10.1% for Chechans. The prevalence of impaired fasting glycemia and diabetes were significantly higher in men, older age groups, married, subjects of lower educational level, past smokers, and subjects with obesity. Low high-density lipoprotein cholesterol was the most common abnormality in the two populations. The homogenous, genetically isolated Circassian and Chechan populations sharing the same environmental influences suggest a role for genetic risk factors for diabetes. Thus these two populations are suitable for additional genetics studies that may lead to the identification of novel risk factors for type 2 diabetes. In addition, more than half of patients with diabetes were with unsatisfactory control. Therefore, they are likely to benefit from programs encouraging healthy weight and physical activity. Copyright © 2012 Elsevier Inc. All rights reserved.

A Genome-Wide Linkage Study for Chronic Obstructive Pulmonary Disease in a Dutch Genetic Isolate Identifies Novel Rare Candidate Variants.

PubMed

Nedeljkovic, Ivana; Terzikhan, Natalie; Vonk, Judith M; van der Plaat, Diana A; Lahousse, Lies; van Diemen, Cleo C; Hobbs, Brian D; Qiao, Dandi; Cho, Michael H; Brusselle, Guy G; Postma, Dirkje S; Boezen, H M; van Duijn, Cornelia M; Amin, Najaf

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a complex and heritable disease, associated with multiple genetic variants. Specific familial types of COPD may be explained by rare variants, which have not been widely studied. We aimed to discover rare genetic variants underlying COPD through a genome-wide linkage scan. Affected-only analysis was performed using the 6K Illumina Linkage IV Panel in 142 cases clustered in 27 families from a genetic isolate, the Erasmus Rucphen Family (ERF) study. Potential causal variants were identified by searching for shared rare variants in the exome-sequence data of the affected members of the families contributing most to the linkage peak. The identified rare variants were then tested for association with COPD in a large meta-analysis of several cohorts. Significant evidence for linkage was observed on chromosomes 15q14-15q25 [logarithm of the odds (LOD) score = 5.52], 11p15.4-11q14.1 (LOD = 3.71) and 5q14.3-5q33.2 (LOD = 3.49). In the chromosome 15 peak, that harbors the known COPD locus for nicotinic receptors, and in the chromosome 5 peak we could not identify shared variants. In the chromosome 11 locus, we identified four rare (minor allele frequency (MAF) <0.02), predicted pathogenic, missense variants. These were shared among the affected family members. The identified variants localize to genes including neuroblast differentiation-associated protein ( AHNAK ), previously associated with blood biomarkers in COPD, phospholipase C Beta 3 ( PLCB3 ), shown to increase airway hyper-responsiveness, solute carrier family 22-A11 ( SLC22A11 ), involved in amino acid metabolism and ion transport, and metallothionein-like protein 5 ( MTL5 ), involved in nicotinate and nicotinamide metabolism. Association of SLC22A11 and MTL5 variants were confirmed in the meta-analysis of 9,888 cases and 27,060 controls. In conclusion, we have identified novel rare variants in plausible genes related to COPD. Further studies utilizing large sample whole-genome sequencing should further confirm the associations at chromosome 11 and investigate the chromosome 15 and 5 linked regions.

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

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.

A Multimethodological Study of Preschoolers' Preferences for Aggressive Television and Video Games.

PubMed

Jamnik, Matthew R; DiLalla, Lisabeth F

2018-01-01

The association between aggressive media and related behavior is complicated, and the role of underlying genetics has not been adequately explored. A better understanding of the role of genetics on the relationship between aggressive media and behavior, especially in young children, is critical. Using a twin/triplets sample (N = 184 children), the authors investigated the association between preschoolers' preferred media choices and their aggressive behaviors. A multimeasure methodology was utilized, examining children's reports of their preferred media games and shows, observed child negativity and aggression in the lab, and parent reports of their own and their children's aggressive behaviors. The results demonstrated a significant relationship between maternal aggression and parent-reported child aggression, especially for boys. Genetic analyses demonstrated significant heritability for children's parent-reported aggressive behaviors, supporting the biological basis of aggression, but not for media aggression preferences. Controlling for genetics, the authors found that the association between media preferences and aggressive behavior may be genetic in origin. These results emphasize the importance of considering shared genetics underlying the relationship between children's aggressive behaviors and their media preferences, as well as environmental influences. By examining preschoolers, the present study provides insight into the importance of media influences in children younger than those previously studied.

Binary Classification using Decision Tree based Genetic Programming and Its Application to Analysis of Bio-mass Data

NASA Astrophysics Data System (ADS)

To, Cuong; Pham, Tuan D.

2010-01-01

In machine learning, pattern recognition may be the most popular task. "Similar" patterns identification is also very important in biology because first, it is useful for prediction of patterns associated with disease, for example cancer tissue (normal or tumor); second, similarity or dissimilarity of the kinetic patterns is used to identify coordinately controlled genes or proteins involved in the same regulatory process. Third, similar genes (proteins) share similar functions. In this paper, we present an algorithm which uses genetic programming to create decision tree for binary classification problem. The application of the algorithm was implemented on five real biological databases. Base on the results of comparisons with well-known methods, we see that the algorithm is outstanding in most of cases.

Host genotype and age shape the leaf and root microbiomes of a wild perennial plant

DOE PAGES

Wagner, Maggie R.; Lundberg, Derek S.; del Rio, Tijana G.; ...

2016-07-12

Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant's genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots of Boechera stricta (Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome ismore » evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.« less

Socialization and Selection Effects in the Association between Weight Conscious Peer Groups and Thin-Ideal Internalization: A Co-Twin Control Study

PubMed Central

Burt, S. Alexandra; O’Connor, Shannon; Thompson, J. Kevin; Klump, Kelly L.

2016-01-01

Affiliation with weight conscious peer groups is theorized to increase thin-ideal internalization through socialization processes. However, selection effects could contribute if genetic and/or environmental predispositions lead to affiliation with weight conscious peers. Co-twin control methodology was used to examine socialization and selection effects in 614 female twins (ages 8–15) from the Michigan State University Twin Registry (MSUTR). Thin-ideal internalization and peer group characteristics were assessed via self-report questionnaires. Results suggested the presence of both socialization and selection effects. In terms of socialization, twins who reported increased exposure to weight conscious peers relative to their co-twins had elevated thin-ideal internalization scores, regardless of zygosity. However, associations between weight conscious peers and thin-ideal internationalization within twin pairs were attenuated, suggesting that genetic and shared environmental selection effects also contribute. Findings significantly extend previous work by confirming the presence of socialization processes and highlighting selection processes to be examined in future longitudinal research. PMID:26859605

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.

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

To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?

PubMed

Jiang, Xia; Frisell, Thomas; Askling, Johan; Karlson, Elizabeth W; Klareskog, Lars; Alfredsson, Lars; Källberg, Henrik

2015-02-01

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA. Copyright © 2015 by the American College of Rheumatology.

Natural re-colonization and admixture of wolves (Canis lupus) in the US Pacific Northwest: challenges for the protection and management of rare and endangered taxa.

PubMed

Hendricks, Sarah A; Schweizer, Rena M; Harrigan, Ryan J; Pollinger, John P; Paquet, Paul C; Darimont, Chris T; Adams, Jennifer R; Waits, Lisette P; vonHoldt, Bridgett M; Hohenlohe, Paul A; Wayne, Robert K

2018-06-07

Admixture resulting from natural dispersal processes can potentially generate novel phenotypic variation that may facilitate persistence in changing environments or result in the loss of population-specific adaptations. Yet, under the US Endangered Species Act, policy is limited for management of individuals whose ancestry includes a protected taxon; therefore, they are generally not protected under the Act. This issue is exemplified by the recently re-established grey wolves of the Pacific Northwest states of Washington and Oregon, USA. This population was likely founded by two phenotypically and genetically distinct wolf ecotypes: Northern Rocky Mountain (NRM) forest and coastal rainforest. The latter is considered potentially threatened in southeast Alaska and thus the source of migrants may affect plans for their protection. To assess the genetic source of the re-established population, we sequenced a ~ 300 bp portion of the mitochondrial control region and ~ 5 Mbp of the nuclear genome. Genetic analysis revealed that the Washington wolves share ancestry with both wolf ecotypes, whereas the Oregon population shares ancestry with NRM forest wolves only. Using ecological niche modelling, we found that the Pacific Northwest states contain environments suitable for each ecotype, with wolf packs established in both environmental types. Continued migration from coastal rainforest and NRM forest source populations may increase the genetic diversity of the Pacific Northwest population. However, this admixed population challenges traditional management regimes given that admixture occurs between an adaptively distinct ecotype and a more abundant reintroduced interior form. Our results emphasize the need for a more precise US policy to address the general problem of admixture in the management of endangered species, subspecies, and distinct population segments.

Genetic analysis of Black Tiger shrimp (Penaeus monodon) across its natural distribution range reveals more recent colonization of Fiji and other South Pacific islands.

PubMed

Waqairatu, Salote S; Dierens, Leanne; Cowley, Jeff A; Dixon, Tom J; Johnson, Karyn N; Barnes, Andrew C; Li, Yutao

2012-08-01

The Black Tiger shrimp (Penaeus monodon) has a natural distribution range from East Africa to the South Pacific Islands. Although previous studies of Indo-Pacific P. monodon have found populations from the Indian Ocean and Australasia to differ genetically, their relatedness to South Pacific shrimp remains unknown. To address this, polymorphisms at eight shared microsatellite loci and haplotypes in a 418-bp mtDNA-CR (control region) sequence were examined across 682 P. monodon from locations spread widely across its natural range, including the South Pacific islands of Fiji, Palau, and Papua New Guinea (PNG). Observed microsatellite heterozygosities of 0.82-0.91, allele richness of 6.85-9.69, and significant mtDNA-CR haplotype variation indicated high levels of genetic diversity among the South Pacific shrimp. Analysis of microsatellite genotypes using a Bayesian STRUCTURE method segregated Indo-Pacific P. monodon into eight distinct clades, with Palau and PNG shrimp clustering among others from Southeast Asia and eastern Australia, respectively, and Fiji shrimp clustering as a distinct group. Phylogenetic analyses of mtDNA-CR haplotypes delineated shrimp into three groupings, with shrimp from Fiji again being distinct by sharing no haplotypes with other populations. Depending on regional location, the genetic structures and substructures identified from the genotyping and mtDNA-CR haplotype phylogeny could be explained by Metapopulation and/or Member-Vagrant type evolutionary processes. Neutrality tests of mutation-drift equilibrium and estimation of the time since population expansion supported a hypothesis that South Pacific P. monodon were colonized from Southeast Asia and eastern Australia during the Pleistocene period over 60,000 years ago when land bridges were more expansive and linked these regions more closely.

Genetic analysis of Black Tiger shrimp (Penaeus monodon) across its natural distribution range reveals more recent colonization of Fiji and other South Pacific islands

PubMed Central

Waqairatu, Salote S; Dierens, Leanne; Cowley, Jeff A; Dixon, Tom J; Johnson, Karyn N; Barnes, Andrew C; Li, Yutao

2012-01-01

The Black Tiger shrimp (Penaeus monodon) has a natural distribution range from East Africa to the South Pacific Islands. Although previous studies of Indo-Pacific P. monodon have found populations from the Indian Ocean and Australasia to differ genetically, their relatedness to South Pacific shrimp remains unknown. To address this, polymorphisms at eight shared microsatellite loci and haplotypes in a 418-bp mtDNA-CR (control region) sequence were examined across 682 P. monodon from locations spread widely across its natural range, including the South Pacific islands of Fiji, Palau, and Papua New Guinea (PNG). Observed microsatellite heterozygosities of 0.82–0.91, allele richness of 6.85–9.69, and significant mtDNA-CR haplotype variation indicated high levels of genetic diversity among the South Pacific shrimp. Analysis of microsatellite genotypes using a Bayesian STRUCTURE method segregated Indo-Pacific P. monodon into eight distinct clades, with Palau and PNG shrimp clustering among others from Southeast Asia and eastern Australia, respectively, and Fiji shrimp clustering as a distinct group. Phylogenetic analyses of mtDNA-CR haplotypes delineated shrimp into three groupings, with shrimp from Fiji again being distinct by sharing no haplotypes with other populations. Depending on regional location, the genetic structures and substructures identified from the genotyping and mtDNA-CR haplotype phylogeny could be explained by Metapopulation and/or Member–Vagrant type evolutionary processes. Neutrality tests of mutation-drift equilibrium and estimation of the time since population expansion supported a hypothesis that South Pacific P. monodon were colonized from Southeast Asia and eastern Australia during the Pleistocene period over 60,000 years ago when land bridges were more expansive and linked these regions more closely. PMID:22957205

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

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.

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

Genetic information: Special or not? Responses from focus groups with members of a health maintenance organization.

PubMed

Diergaarde, Brenda; Bowen, Deborah J; Ludman, Evette J; Culver, Julie O; Press, Nancy; Burke, Wylie

2007-03-15

Genetic information is used increasingly in health care. Some experts have argued that genetic information is qualitatively different from other medical information and, therefore, raises unique social issues. This view, called "genetic exceptionalism," has importantly influenced recent policy efforts. Others have argued that genetic information is like other medical information and that treating it differently may actually result in unintended disparities. Little is known about how the general public views genetic information. To identify opinions about implications of genetic and other medical information among the general population, we conducted a series of focus groups in Seattle, WA. Participants were women and men between ages 18 and 74, living within 30 miles of Seattle and members of the Group Health Cooperative. A structured discussion guide was used to ensure coverage of all predetermined topics. Sessions lasted approximately 2 hr; were audio taped and transcribed. The transcripts formed the basis of the current analysis. Key findings included the theme that genetic information was much like other medical information and that all sensitive medical information should be well protected. Personal choice (i.e., the right to choose whether to know health risk information and to control who else knows) was reported to be of crucial importance. Participants had an understanding of the tensions involved in protecting privacy versus sharing medical information to help another person. These data may guide future research and policy concerning the use and protection of medical information, including genetic information. (c) 2007 Wiley-Liss, Inc.

Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

PubMed Central

Hernández-Díaz, Sonia; Levin, Michael

2014-01-01

Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome

PubMed Central

2013-01-01

Background Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Methods Two previously published blood gene expression data sets – the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members) – were analyzed. All individuals of each dataset were projected to biological pathways, and each sample’s Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Results Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Conclusions Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression signal, and showed that outlier groups were distinct for each implicated pathway. Moreover, our results suggest that by seeking heterogeneity, pathway-based outlier analysis can reveal expression signals that are not apparent when considering only shared group differences. PMID:24063311

Peripheral blood gene expression signature differentiates children with autism from unaffected siblings

PubMed Central

Kong, SW; Shimizu-Motohashi, Y; Campbell, MG; Lee, IH; Collins, CD; Brewster, SJ; Holm, IA; Rappaport, L

2013-01-01

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. One hundred eighty nine genes were significantly differentially expressed between proband-sib pairs (nominal p-value < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, 5 of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin. PMID:23625158

4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

PubMed

Jirholt, Johan; Asling, Bengt; Hammond, Paul; Davidson, Geoffrey; Knutsson, Mikael; Walentinsson, Anna; Jensen, Jörgen M; Lehmann, Anders; Agreus, Lars; Lagerström-Fermer, Maria

2011-04-28

Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P(adj) = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3 ± 11.4 % (p = 0.007) and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.

Genetic liability for schizophrenia predicts risk of immune disorders.

PubMed

Stringer, Sven; Kahn, René S; de Witte, Lot D; Ophoff, Roel A; Derks, Eske M

2014-11-01

Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes. We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively. Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05). Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis.

PubMed

Choi, Yong Jun; Song, Insun; Jin, Yilan; Jin, Hyun-Seok; Ji, Hyung Min; Jeong, Seon-Yong; Won, Ye-Yeon; Chung, Yoon-Sok

2017-10-20

Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p=0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p=0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population

PubMed Central

de Kovel, Carolien G.; Mulder, Flip; van Setten, Jessica; van ‘t Slot, Ruben; Al-Rubaish, Abdullah; Alshehri, Abdullah M.; Al Faraidy, Khalid; Al-Ali, Abdullah; Al-Madan, Mohammed; Al Aqaili, Issa; Larbi, Emmanuel; Al-Ali, Rudaynah; Alzahrani, Alhusain; Asselbergs, Folkert W.; Koeleman, Bobby P. C.; Al-Ali, Amein

2016-01-01

Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations. PMID:26849363

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.

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.

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.

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.

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.

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.

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.

The impact of past climate change on genetic variation and population connectivity in the Icelandic arctic fox

PubMed Central

Mellows, Andrew; Barnett, Ross; Dalén, Love; Sandoval-Castellanos, Edson; Linderholm, Anna; McGovern, Thomas H.; Church, Mike J.; Larson, Greger

2012-01-01

Previous studies have suggested that the presence of sea ice is an important factor in facilitating migration and determining the degree of genetic isolation among contemporary arctic fox populations. Because the extent of sea ice is dependent upon global temperatures, periods of significant cooling would have had a major impact on fox population connectivity and genetic variation. We tested this hypothesis by extracting and sequencing mitochondrial control region sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth-century AD archaeological sites in northeast Iceland, both of which predate the Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that five haplotypes have been observed in modern Icelandic foxes, a single haplotype was shared among all of the ancient individuals. Results from simulations within an approximate Bayesian computation framework suggest that the rapid increase in Icelandic arctic fox haplotype diversity can only be explained by sea-ice-mediated fox immigration facilitated by the Little Ice Age. PMID:22977155

The impact of past climate change on genetic variation and population connectivity in the Icelandic arctic fox.

PubMed

Mellows, Andrew; Barnett, Ross; Dalén, Love; Sandoval-Castellanos, Edson; Linderholm, Anna; McGovern, Thomas H; Church, Mike J; Larson, Greger

2012-11-22

Previous studies have suggested that the presence of sea ice is an important factor in facilitating migration and determining the degree of genetic isolation among contemporary arctic fox populations. Because the extent of sea ice is dependent upon global temperatures, periods of significant cooling would have had a major impact on fox population connectivity and genetic variation. We tested this hypothesis by extracting and sequencing mitochondrial control region sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth-century AD archaeological sites in northeast Iceland, both of which predate the Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that five haplotypes have been observed in modern Icelandic foxes, a single haplotype was shared among all of the ancient individuals. Results from simulations within an approximate Bayesian computation framework suggest that the rapid increase in Icelandic arctic fox haplotype diversity can only be explained by sea-ice-mediated fox immigration facilitated by the Little Ice Age.

Twin studies advance the understanding of gene-environment interplay in human nutrigenomics.

PubMed

Pallister, Tess; Spector, Tim D; Menni, Cristina

2014-12-01

Investigations into the genetic architecture of diet-disease relationships are particularly relevant today with the global epidemic of obesity and chronic disease. Twin studies have demonstrated that genetic makeup plays a significant role in a multitude of dietary phenotypes such as energy and macronutrient intakes, dietary patterns, and specific food group intakes. Besides estimating heritability of dietary assessment, twins provide a naturally unique, case-control experiment. Due to their shared upbringing, matched genes and sex (in the case of monozygotic (MZ) twin pairs), and age, twins provide many advantages over classic epidemiological approaches. Future genetic epidemiological studies could benefit from the twin approach particularly where defining what is 'normal' is problematic due to the high inter-individual variability underlying metabolism. Here, we discuss the use of twins to generate heritability estimates of food intake phenotypes. We then highlight the value of discordant MZ pairs to further nutrition research through discovery and validation of biomarkers of intake and health status in collaboration with cutting-edge omics technologies.

Differential association of family subsystem negativity on siblings' maladjustment: using behavior genetic methods to test process theory.

PubMed

Feinberg, Mark E; Reiss, David; Neiderhiser, Jenae M; Hetherington, E Mavis

2005-12-01

This study investigated the family context of adolescent sibling similarity and differentiation in maladjustment (antisocial behavior and depression) by examining negativity in different subsystems. Two hypotheses were proposed: (1) Parental and sibling negativity tends to diffuse through the family system, especially because of the high level of reciprocity in sibling relationships, leading to sibling similarity; and (2) interparental (coparenting) conflict disrupts cohesive functioning and thereby motivates and facilitates sibling differentiation and niche picking. To control for the effects of similar genes between siblings, the authors used behavioral genetic models with a genetically informed sample of 720 two-parent families, each with at least 2 adolescent siblings. Results for the differences in shared environmental influences across groups high and low in each of the domains of family negativity provided partial support for the hypotheses. The results further understanding of influences on individual differences and support a theory of how parent-child and interparental relationships intersect with sibling relationship dynamics. Copyright 2006 APA, all rights reserved).

Morphological adaptation with no mitochondrial DNA differentiation in the coastal plain swamp sparrow

USGS Publications Warehouse

Greenberg, R.; Cordero, P.J.; Droege, S.; Fleischer, R.C.

1998-01-01

We estimated genetic differentiation between morphologically distinct tidal marsh populations of Swamp Sparrows (Melospiza georgiana nigrescens) and the more widespread inland populations (M. g. georgiana and M. g. ericrypta). The tidal marsh populations are consistently grayer with more extensive black markings (particularly in the crown), and their bills are larger. These differences are variously shared with other species of salt marsh birds and small mammals. We analyzed mitochondrial DNA sequences (5′ end of control region, COII/t-lys/ATPase8, and ND2) of Swamp Sparrows and found low levels of genetic variation and no evidence of geographic structure. These results suggest a rapid and recent geographic expansion of Swamp Sparrows from restricted Pleistocene populations. Morphological differentiation has occurred without long-term genetic isolation, suggesting that selection on the divergent traits is intense. The grayer and more melanistic plumage is probably cryptic coloration for foraging on tidal mud, which tends to be grayish as a result of the formation of iron sulfides, rather than iron oxides, under anaerobic conditions.

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

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.

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.

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case–control study

PubMed Central

Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P.; Markus, Hugh S.; Lewis, Cathryn M.

2017-01-01

Abstract Objectives. To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. Methods. A case–control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. Results. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 −7). HLA haplotype ORs in European and African ancestry individuals were highly correlated (r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 −4). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 −4) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 −5) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 −3). Conclusion. Gene–environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. PMID:28407095

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.

PubMed

Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P; Markus, Hugh S; Lewis, Cathryn M; Scott, Ian C

2017-08-01

To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. A case-control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 - 7 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 - 5 ) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 - 3 ). Gene-environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Identification of Four Novel Loci in Asthma in European American and African American Populations.

PubMed

Almoguera, Berta; Vazquez, Lyam; Mentch, Frank; Connolly, John; Pacheco, Jennifer A; Sundaresan, Agnes S; Peissig, Peggy L; Linneman, James G; McCarty, Catherine A; Crosslin, David; Carrell, David S; Lingren, Todd; Namjou-Khales, Bahram; Harley, John B; Larson, Eric; Jarvik, Gail P; Brilliant, Murray; Williams, Marc S; Kullo, Iftikhar J; Hysinger, Erik B; Sleiman, Patrick M A; Hakonarson, Hakon

2017-02-15

Despite significant advances in knowledge of the genetic architecture of asthma, specific contributors to the variability in the burden between populations remain uncovered. To identify additional genetic susceptibility factors of asthma in European American and African American populations. A phenotyping algorithm mining electronic medical records was developed and validated to recruit cases with asthma and control subjects from the Electronic Medical Records and Genomics network. Genome-wide association analyses were performed in pediatric and adult asthma cases and control subjects with European American and African American ancestry followed by metaanalysis. Nominally significant results were reanalyzed conditioning on allergy status. The validation of the algorithm yielded an average of 95.8% positive predictive values for both cases and control subjects. The algorithm accrued 21,644 subjects (65.83% European American and 34.17% African American). We identified four novel population-specific associations with asthma after metaanalyses: loci 6p21.31, 9p21.2, and 10q21.3 in the European American population, and the PTGES gene in African Americans. TEK at 9p21.2, which encodes TIE2, has been shown to be involved in remodeling the airway wall in asthma, and the association remained significant after conditioning by allergy. PTGES, which encodes the prostaglandin E synthase, has also been linked to asthma, where deficient prostaglandin E 2 synthesis has been associated with airway remodeling. This study adds to understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.

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.

Neighborhood walkability moderates the association between low back pain and physical activity: A co-twin control study.

PubMed

Zadro, J R; Shirley, D; Pinheiro, M B; Bauman, A; Duncan, G E; Ferreira, P H

2017-06-01

The aim of this study was to investigate whether neighborhood walkability moderates the association between low back pain (LBP) and physical activity (PA), using a co-twin design to control for genetics and shared environmental factors. A cross-sectional analysis was performed on 10,228 twins from the Washington State Twin Registry with available data on LBP from recruitment surveys between 2009 and 2013. LBP within the past 3months was our exposure variable. Our outcome variables were sufficient moderate or vigorous-intensity PA (MVPA, defined as at least 75min of vigorous-intensity PA, or 150min of moderate-intensity PA per week), and walking (≥150min per week). Neighborhood walkability, estimated using the commercially available Walk Score®, was our moderator variable. After controlling for the influence of genetics and shared environment, individuals reporting LBP were significantly less likely to engage in sufficient MVPA if they lived in a neighborhood with high walkability (OR=0.59, 95%CI: 0.36-0.96). There was no association between LBP and sufficient MVPA for individuals living in a neighborhood with low walkability (OR=1.27, 95%CI: 0.93-1.72), demonstrating that walkability is a significant moderator of the association between LBP and PA (interaction p=0.013). These findings were similar for the association between LBP and walking (high walkability OR=0.42, 95%CI: 0.22-0.78; low walkability OR=0.71, 95%CI: 0.46-1.12), although the interaction was not significant (p=0.700). Neighborhood walkability moderates the association between LBP and PA. Our results highlight the importance of targeting interventions promoting PA towards individuals with LBP living in a neighborhood with good walkable access to amenities. Copyright © 2017 Elsevier Inc. All rights reserved.

GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

PubMed Central

Skibola, Christine F.; Darabi, Hatef; Conde, Lucia; Hjalgrim, Henrik; Kumar, Vikrant; Chang, Ellen T.; Rothman, Nathaniel; Cerhan, James R.; Brooks-Wilson, Angela R.; Rehnberg, Emil; Irwan, Ishak D.; Ryder, Lars P.; Brown, Peter N.; Bracci, Paige M.; Agana, Luz; Riby, Jacques; Cozen, Wendy; Davis, Scott; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Wang, Sophia S.; Slager, Susan L.; Fredericksen, Zachary S.; Novak, Anne J.; Kay, Neil E.; Habermann, Thomas M.; Armstrong, Bruce; Kricker, Anne; Milliken, Sam; Purdue, Mark P.; Vajdic, Claire M.; Boyle, Peter; Lan, Qing; Zahm, Shelia H.; Zhang, Yawei; Zheng, Tongzhang; Leach, Stephen; Spinelli, John J.; Smith, Martyn T.; Chanock, Stephen J.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Glimelius, Bengt; Melbye, Mads; Liu, Edison T.; Adami, Hans-Olov; Humphreys, Keith; Liu, Jianjun

2011-01-01

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL. PMID:21533074

Variation of partial transferrin sequences and phylogenetic relationships among hares (Lepus capensis, Lagomorpha) from Tunisia.

PubMed

Awadi, Asma; Suchentrunk, Franz; Makni, Mohamed; Ben Slimen, Hichem

2016-10-01

North African hares are currently included in cape hares, Lepus capensis sensu lato, a taxon that may be considered a superspecies or a complex of closely related species. The existing molecular data, however, are not unequivocal, with mtDNA control region sequences suggesting a separate species status and nuclear loci (allozymes, microsatellites) revealing conspecificity of L. capensis and L. europaeus. Here, we study sequence variation in the intron 6 (468 bp) of the transferrin nuclear gene, of 105 hares with different coat colour from different regions in Tunisia with respect to genetic diversity and differentiation, as well as their phylogenetic status. Forty-six haplotypes (alleles) were revealed and compared phylogenetically to all available TF haplotypes of various Lepus species retrieved from GenBank. Maximum Likelihood, neighbor joining and median joining network analyses concordantly grouped all currently obtained haplotypes together with haplotypes belonging to six different Chinese hare species and the African scrub hare L. saxatilis. Moreover, two Tunisian haploypes were shared with L. capensis, L timidus, L. sinensis, L. yarkandensis, and L. hainanus from China. These results indicated the evolutionary complexity of the genus Lepus with the mixing of nuclear gene haplotypes resulting from introgressive hybridization or/and shared ancestral polymorphism. We report the presence of shared ancestral polymorphism between North African and Chinese hares. This has not been detected earlier in the mtDNA sequences of the same individuals. Genetic diversity of the TF sequences from the Tunisian populations was relatively high compared to other hare populations. However, genetic differentiation and gene flow analyses (AMOVA, F ST , Nm) indicated little divergence with the absence of geographically meaningful phylogroups and lack of clustering with coat colour types. These results confirm the presence of a single hare species in Tunisia, but a sound inference on its phylogenetic position would require additional nuclear markers and numerous geographically meaningful samples from Africa and Eurasia.

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

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.

Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post-orthodontic root resorption in endodontic and their contralateral vital control teeth differently.

PubMed

Iglesias-Linares, A; Yañez-Vico, R M; Ballesta, S; Ortiz-Ariza, E; Mendoza-Mendoza, A; Perea, E; Solano-Reina, E

2012-11-01

To investigate whether the genetic variants of the interleukin-1 gene cluster (IL1) are associated with a possible genetically induced variability in post-orthodontic external apical root resorption (EARR) in root filled teeth and their control counterparts with vital pulps. One hundred and forty-six maxillary premolars were evaluated radiographically following orthodontic treatment. Genetic screening was performed on orthodontic patients for two single-nucleotide polymorphisms (SNPs: rs1800587 and rs1143634) in the IL1 gene cluster. Subjects were divided into two groups according to the presence or absence of radiographic post-orthodontic EARR (>2 mm) in root filled teeth and their controls with vital pulps. Logistic regression analysis was performed to obtain an adjusted estimation between EARR and IL1 polymorphisms. Allelic frequencies, genotype distributions, and adjusted odds ratio (OR), at 95% confidence interval, were also calculated. Whilst no clear statistical association was found for gene variations in IL1A, a sound association was found in the comparative analysis of subjects homozygous [2/2(TT)] for the IL1B gene, which resulted in a two times increased risk of suffering post-orthodontic EARR in root filled teeth [OR, 2.032 (P = 0.031); CI,1.99-14.77] when compared with their controls with vital pulps. There was, however, a shared predisposition to EARR in controls with vital pulps and root filled teeth of subjects homozygous for allele 1 [OR, 5.05 (P = 0.002)] and [OR, 2.77 (P = 0.037)], respectively. Genetic variations in the interleukin-1β gene (rs1143634) predispose root filled teeth to EARR for matched pairs secondary to orthodontic treatment in a different way from their control teeth with vital pulps in subjects homozygous for allele 2 [2/2(TT)]. © 2012 International Endodontic Journal.

Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution.

PubMed

Allen-Brady, Kristina; Firszt, Rafael; Fang, John C; Wong, Jathine; Smith, Ken R; Peterson, Kathryn A

2017-10-01

Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease.

PubMed

Hui, Ken Y; Fernandez-Hernandez, Heriberto; Hu, Jianzhong; Schaffner, Adam; Pankratz, Nathan; Hsu, Nai-Yun; Chuang, Ling-Shiang; Carmi, Shai; Villaverde, Nicole; Li, Xianting; Rivas, Manual; Levine, Adam P; Bao, Xiuliang; Labrias, Philippe R; Haritunians, Talin; Ruane, Darren; Gettler, Kyle; Chen, Ernie; Li, Dalin; Schiff, Elena R; Pontikos, Nikolas; Barzilai, Nir; Brant, Steven R; Bressman, Susan; Cheifetz, Adam S; Clark, Lorraine N; Daly, Mark J; Desnick, Robert J; Duerr, Richard H; Katz, Seymour; Lencz, Todd; Myers, Richard H; Ostrer, Harry; Ozelius, Laurie; Payami, Haydeh; Peter, Yakov; Rioux, John D; Segal, Anthony W; Scott, William K; Silverberg, Mark S; Vance, Jeffery M; Ubarretxena-Belandia, Iban; Foroud, Tatiana; Atzmon, Gil; Pe'er, Itsik; Ioannou, Yiannis; McGovern, Dermot P B; Yue, Zhenyu; Schadt, Eric E; Cho, Judy H; Peter, Inga

2018-01-10

Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10 -10 ) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10 -8 ). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Ethical issues in psychiatric genetics.

PubMed

Appelbaum, Paul S

2004-11-01

As knowledge grows regarding the genetic bases of psychiatric disorders, a variety of ethical issues will need to be confronted. Current evidence suggests that the etiology of most psychiatric disorders rests on a combination of multiple genes and environmental factors. As tests for the genes involved become more easily available, pressures will arise to use them for prenatal testing, screening of children and adults, selection of potential adoptees, and pre-marital screening. Common problems that will need to be addressed include popular misunderstanding of the consequences of possessing an affected allele, impact of knowledge of one's genetic make-up on one's sense of self, and the discriminatory use of genetic information to deny persons access to insurance and employment. Although most states have some legislation aimed at preventing discrimination, the laws' coverage is spotty and federal rules are lacking. Physicians may find that newly available genetic information creates new duties for them, including warning third parties who may share the patient's genetic endowment. And genetics research itself has raised questions about when to disclose information to subjects and their family members about the genes that are being studied, and how to define the subjects of the research when information is collected about family members other than the proband. Knowledge of these dilemmas is a first step to resolving them, something that the medical profession will need to attend to in the near-term. Neglect will lead others to set the rules that will control medical practice, including the practice of psychiatry, in the new world of genetic medicine.

HUGO urges genetic benefit-sharing.

PubMed

2000-01-01

In view of the fact that for-profit enterprise exceeds public expenditures on genetic research and that benefits from the Human Genome Project may accrue only to rich people in rich nations, the HUGO Ethics Committee discussed the necessity of benefit-sharing. Discussions involved case examples ranging from single-gene to multi-factorial disorders and included the difficulties of defining community, especially when multifactorial diseases are involved. The Committee discussed arguments for benefit-sharing, including common heritage, the genome as a common resource, and three types of justice: compensatory, procedural, and distributive. The Committee also discussed the importance of community participation in defining benefit, agreed that companies involved in health have special obligations beyond paying taxes, and recommended they devote 1-3% of net profits to healthcare infrastructure or humanitarian efforts.

Lung Cancer: One Disease or Many.

PubMed

O'Brien, Timothy D; Jia, Peilin; Aldrich, Melinda C; Zhao, Zhongming

2018-06-05

Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC). These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes. This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future. © 2018 S. Karger AG, Basel.

Sherpas share genetic variations with Tibetans for high-altitude adaptation.

PubMed

Bhandari, Sushil; Zhang, Xiaoming; Cui, Chaoying; Yangla; Liu, Lan; Ouzhuluobu; Baimakangzhuo; Gonggalanzi; Bai, Caijuan; Bianba; Peng, Yi; Zhang, Hui; Xiang, Kun; Shi, Hong; Liu, Shiming; Gengdeng; Wu, Tianyi; Qi, Xuebin; Su, Bing

2017-01-01

Sherpas, a highlander population living in Khumbu region of Nepal, are well known for their superior climbing ability in Himalayas. However, the genetic basis of their adaptation to high-altitude environments remains elusive. We collected DNA samples of 582 Sherpas from Nepal and Tibetan Autonomous Region of China, and we measured their hemoglobin levels and degrees of blood oxygen saturation. We genotyped 29 EPAS1 SNPs, two EGLN1 SNPs and the TED polymorphism (3.4 kb deletion) in Sherpas. We also performed genetic association analysis among these sequence variants with phenotypic data. We found similar allele frequencies on the tested 32 variants of these genes in Sherpas and Tibetans. Sherpa individuals carrying the derived alleles of EPAS1 (rs113305133, rs116611511 and rs12467821), EGLN1 (rs186996510 and rs12097901) and TED have lower hemoglobin levels when compared with those wild-type allele carriers. Most of the EPAS1 variants showing significant association with hemoglobin levels in Tibetans were replicated in Sherpas. The shared sequence variants and hemoglobin trait between Sherpas and Tibetans indicate a shared genetic basis for high-altitude adaptation, consistent with the proposal that Sherpas are in fact a recently derived population from Tibetans and they inherited adaptive variants for high-altitude adaptation from their Tibetan ancestors.

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.

HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

PubMed

Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

2018-04-01

HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

Hybridization among Arctic white-headed gulls (Larus spp.) obscures the genetic legacy of the Pleistocene

USGS Publications Warehouse

Sonsthagen, Sarah A.; Chesser, R. Terry; Bell, Douglas A.; Dove, Carla J.

2012-01-01

We studied the influence of glacial oscillations on the genetic structure of seven species of white-headed gull that breed at high latitudes (Larus argentatus, L. canus, L. glaucescens, L. glaucoides, L. hyperboreus, L. schistisagus, and L. thayeri). We evaluated localities hypothesized as ice-free areas or glacial refugia in other Arctic vertebrates using molecular data from 11 microsatellite loci, mitochondrial DNA (mtDNA) control region, and six nuclear introns for 32 populations across the Holarctic. Moderate levels of genetic structure were observed for microsatellites (FST= 0.129), introns (ΦST= 0.185), and mtDNA control region (ΦST= 0.461), with among-group variation maximized when populations were grouped based on subspecific classification. Two haplotype and at least two allele groups were observed across all loci. However, no haplotype/allele group was composed solely of individuals of a single species, a pattern consistent with recent divergence. Furthermore, northernmost populations were not well differentiated and among-group variation was maximized when L. argentatus and L. hyberboreus populations were grouped by locality rather than species, indicating recent hybridization. Four populations are located in putative Pleistocene glacial refugia and had larger t estimates than the other 28 populations. However, we were unable to substantiate these putative refugia using coalescent theory, as all populations had genetic signatures of stability based on mtDNA. The extent of haplotype and allele sharing among Arctic white-headed gull species is noteworthy. Studies of other Arctic taxa have generally revealed species-specific clusters as well as genetic structure within species, usually correlated with geography. Aspects of white-headed gull behavioral biology, such as colonization ability and propensity to hybridize, as well as their recent evolutionary history, have likely played a large role in the limited genetic structure observed.

Mapping the Regional Influence of Genetics on Brain Structure Variability - A Tensor-Based Morphometry Study

PubMed Central

Brun, Caroline; Leporé, Natasha; Pennec, Xavier; Lee, Agatha D.; Barysheva, Marina; Madsen, Sarah K.; Avedissian, Christina; Chou, Yi-Yu; de Zubicaray, Greig I.; McMahon, Katie; Wright, Margaret; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Genetic and environmental factors influence brain structure and function profoundly The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins’ 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject’s anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions which have a more protracted maturational time-course. PMID:19446645

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

Treesearch

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

2017-01-01

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...

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

PubMed Central

Laugesen, E; Østergaard, J A; Leslie, R D G

2015-01-01

Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. What’s new? Latent autoimmune diabetes of the adult (LADA) is an autoimmune diabetes defined by adult-onset, presence of diabetes associated autoantibodies, and no insulin treatment requirement for a period after diagnosis. Immunologically, glutamic acid decarboxylase 65 autoantibodies are by far the most common autoantibody in adult-onset diabetes. LADA is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. LADA shares genetic features with both type 1 and type 2 diabetes. Phenotypically, LADA patients are often misdiagnosed as having type 2 diabetes. LADA patients generally have worse HbA1c levels than type 2 diabetes patients. Clinically, LADA patients tend to have a lower mean age at diabetes onset, lower body mass index and more frequent need for insulin treatment than patients with type 2 diabetes. Management of LADA may require a dedicated strategy, yet currently there is a paucity of randomized controlled trial data. PMID:25601320

The etiologic role of genetic and environmental factors in criminal behavior as determined from full- and half-sibling pairs: an evaluation of the validity of the twin method.

PubMed

Kendler, K S; Lönn, S L; Maes, H H; Sundquist, J; Sundquist, K

2015-07-01

Twin studies have shown that criminal behavior (CB) is influenced by both genetic and shared environmental factors. Could these results be replicated using full-siblings and half-siblings? In 911 009 full-siblings reared together (FSRT), 41 872 half-siblings reared together (HSRT) and 52 590 half-siblings reared apart (HSRA), CB was assessed from the Swedish Crime Register. Modeling, including testing for age differences and rearing status, was performed using the OpenMx package. Five sibling models were fitted examining FSRT and HSRT 0-2 years different in age, and both FSRT and HSRT, and FSRT, HSRT and HSRA 0-10 years different in age with and without a specified shared environment indexing age differences. Heritability estimates for CB ranged from 33 to 55% in females and 39 to 56% in males, similar to those found in our prior twin study on the same population. Estimates for the shared environment varied from 1 to 14% in females and 10 to 23% in males, lower than those estimated in the twin study. The specified shared environment indexed by sibling age differences was significant in all models tested. Heritability estimates for CB from full- and half-siblings closely approximated those found from twins in the same population, validating the twin method. Shared environmental estimates were lower, suggesting the presence of shared environmental factors for CB specific to twins. When rearing status can be assessed, full- and half-siblings offer an additional method for assessing the role of genetic and environmental factors in complex disorders. However, age differences in siblings may need to be included in the models.

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.

National human genome projects: an update and an agenda.

PubMed

An, Joon Yong

2017-01-01

Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions in defined population. This perspective summarizes national genome projects conducted in the past 10 years and introduces case studies to utilize genomic data in genetic research.

Shared decision-making, gender and new technologies.

PubMed

Zeiler, Kristin

2007-09-01

Much discussion of decision-making processes in medicine has been patient-centred. It has been assumed that there is, most often, one patient. Less attention has been given to shared decision-making processes where two or more patients are involved. This article aims to contribute to this special area. What conditions need to be met if decision-making can be said to be shared? What is a shared decision-making process and what is a shared autonomous decision-making process? Why make the distinction? Examples are drawn from the area of new reproductive medicine and clinical genetics. Possible gender-differences in shared decision-making are discussed.

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.

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study.

PubMed

Knopik, Valerie S; Sparrow, Elizabeth P; Madden, Pamela A F; Bucholz, Kathleen K; Hudziak, James J; Reich, Wendy; Slutske, Wendy S; Grant, Julia D; McLaughlin, Tara L; Todorov, Alexandre; Todd, Richard D; Heath, Andrew C

2005-05-01

Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

A Twin Study of Heritable and Shared Environmental Contributions to Autism

ERIC Educational Resources Information Center

Frazier, Thomas W.; Thompson, Lee; Youngstrom, Eric A.; Law, Paul; Hardan, Antonio Y.; Eng, Charis; Morris, Nathan

2014-01-01

The present study examined genetic and shared environment contributions to quantitatively-measured autism symptoms and categorically-defined autism spectrum disorders (ASD). Participants included 568 twins from the Interactive Autism Network. Autism symptoms were obtained using the Social Communication Questionnaire and Social Responsiveness…