Using genetic information from candidate gene and genome‐wide association studies in risk prediction for alcohol dependence

Yan, Jia; Alıev, Fazil; Webb, Bradley T.; Kendler, Kenneth S.; Williamson, Vernell; Edenberg, Howard J.; Agrawal, Arpana; Kos, Mark Z.; Almasy, Laura; Nürnberger, John I.; Schuckit, Marc A.; Kramer, John; Rice, John P.; Kuperman, Samuel; Goate, Alison M.; Tischfield, Jay A.; Porjesz, Bernice; Dick, Danielle M.

doi:10.1111/adb.12035

Cited by 45 publications

(37 citation statements)

References 47 publications

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“…Despite enthusiasm for using genome-wide information for personalized medicine (Hamburg & Collins, 2010), our results echo the conclusions from previous work (Yan et al, 2013) that it would be premature to use empirically-derived polygenic scores to predict an individual's risk for developing externalizing disorders. Rather, our results highlight the potential clinical utility of environmentally focused preventions and interventions for moderating genetic predispositions toward externalizing disorders.…”

Section: Discussionsupporting

confidence: 79%

Polygenic Risk for Externalizing Disorders

Salvatore

Alıev

Bucholz³

et al. 2014

Clinical Psychological Science

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In this project, we aimed to bring large-scale gene identification findings into a developmental psychopathology framework. Using a family-based sample, we tested whether polygenic scores for externalizing disorders—based on single nucleotide polymorphism weights derived from genome-wide association study results in adults (n = 1,249)—predicted externalizing disorders, subclinical externalizing behavior, and impulsivity-related traits adolescents (n = 248) and young adults (n = 207), and whether parenting and peer factors in adolescence moderated polygenic risk to predict externalizing disorders. Polygenic scores predicted externalizing disorders in adolescents and young adults, even after controlling for parental externalizing disorder history. Polygenic scores also predicted subclinical externalizing behavior and impulsivity traits in the adolescents and young adults. Adolescent parental monitoring and peer substance use moderated polygenic scores to predict externalizing disorders. This illustrates how state of the science genetics can be integrated with psychological science to identify how genetic risk contributes to the development of psychopathology.

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Section: Discussionsupporting

confidence: 79%

Polygenic Risk for Externalizing Disorders

Salvatore

Alıev

Bucholz³

et al. 2014

Clinical Psychological Science

Self Cite

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“…Other study designs could involve multiple genetic variants through the use of genetic ancestry or admixture mapping approaches (Choudhry et al , 2007) or polygenic risk scores (Salvatore et al , 2014) to examine gene-by-environment interactions in association with alcohol dependence. A better understanding of the genetic architecture of alcohol dependence may be required before polygenic scores out preform family history (Yan et al , 2014). Opportunities to test higher order measured gene-by-environment interactions may require the added collection of genetic data in coordination with ongoing epidemiologic studies.…”

Section: Discussionmentioning

confidence: 99%

Interrelationship between family history of alcoholism and generational status in the prediction of alcohol dependence in US Hispanics

2016

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Background Both a family history of alcoholism and migration-related factors like U.S. versus foreign nativity increase the risk for developing alcohol use disorders in Hispanic Americans. For this study, we integrated these two lines of research to test whether the relationship between familial alcoholism and alcohol dependence changes with successive generations in the U.S. Methods Data were from the wave 1 and wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Subjects self-identified Hispanic ethnicity (N = 4,122; n = 1,784 first, n = 1,169 second, and n = 1,169 third or later generation) and reported ever consuming 12 or more drinks in a one-year period. A family history of alcoholism was assessed in first and second degree relatives. Analyses predicting the number of alcohol dependence symptoms were path models. Results Alcohol dependence symptoms were associated with a stronger family history of alcoholism and later generational status. There was a significant interaction effect between familial alcoholism and generational status; the relationship of familial alcoholism with alcohol dependence symptoms increased significantly with successive generations in the U.S., more strongly in women than men. Acculturation partially mediated the interaction effect between familial alcoholism and generational status on alcohol dependence, although not in the expected direction. Conclusions Familial alcoholism interacted with generational status in predicting alcohol dependence symptoms in U.S. Hispanic drinkers. This relationship suggests that heritability for alcoholism is influenced by a higher order environmental factor, likely characterized by a relaxing of social restrictions on drinking.

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“…Yan et al (2014) used the SAGE EA and COGA EA datasets to conduct risk profile scoring analyses for both a set of candidate gene SNPs and SNPs from the GWAS using various P -value thresholds. In the first analysis, using a set of 21 SNPs associated with AD from candidate gene studies in the family-based COGA dataset to predict AD, they found no association with AD in either the COGA or SAGE samples.…”

Section: Snp Heritability and Genomic Risk Profile Scoring Methodsmentioning

confidence: 99%

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses

Hart

Kranzler

2015

Alcohol Clin Exp Res

108

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Background Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene-based, and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) have improved the detection of specific loci associated with complex traits, including AD. However, findings from GWAS explain only a small proportion of phenotypic variance and alternative methods have been proposed to investigate the associations that do not meet strict genome-wide significance criteria. Methods This review summarizes all published AD GWAS and post-GWAS analyses that have sought to exploit GWAS data to identify AD-associated loci. Results Findings from AD GWAS have been largely inconsistent, with the exception of variants encoding the alcohol metabolizing enzymes. Analyses of GWAS data that go beyond single SNP association testing have demonstrated the polygenic nature of AD and the large contribution of common variants to risk, nominating novel genes and pathways for AD susceptibility. Conclusions Findings from AD GWAS and post-GWAS analyses have greatly increased our understanding of the genetic etiology of AD. However, it is clear that larger samples will be necessary to detect loci in addition to those that encode alcohol metabolizing enzymes, which may only be possible through consortium-based efforts. Post-GWAS approaches to studying the genetic influences on AD are increasingly common and could greatly increase our knowledge of both the genetic architecture of AD and the specific genes and pathways that influence risk.

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Using genetic information from candidate gene and genome‐wide association studies in risk prediction for alcohol dependence

Cited by 45 publications

References 47 publications

Polygenic Risk for Externalizing Disorders

Polygenic Risk for Externalizing Disorders

Interrelationship between family history of alcoholism and generational status in the prediction of alcohol dependence in US Hispanics

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses

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