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Biol Psychiatry. 2011 Sep 15;70(6):513-8. doi: 10.1016/j.biopsych.2011.02.028. Epub 2011 May 6.

A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications.

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  • 1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. aheath@wustl.edu

Abstract

BACKGROUND:

Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence.

METHODS:

Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data.

RESULTS:

No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk.

CONCLUSIONS:

We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).

Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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PMID:
21529783
[PubMed - indexed for MEDLINE]
PMCID:
PMC3210694
Free PMC Article

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