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

Autor: Hart AB; Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Kranzler HR; Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; VISN 4 MIRECC, Philadelphia VAMC, Philadelphia, Pennsylvania.
Jazyk: angličtina
Zdroj: Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2015 Aug; Vol. 39 (8), pp. 1312-27. Date of Electronic Publication: 2015 Jun 25.
DOI: 10.1111/acer.12792
Abstrakt: 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 standard 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.
(Copyright © 2015 by the Research Society on Alcoholism.)
Databáze: MEDLINE
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