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Sunday, June 9, 2013

A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.

Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption.

We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case–control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE).

The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10−6) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10−7), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10−7) and PLCL1 genes (p = 4.1 × 10−6) with maxdrinks.

A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis.

The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10−4) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10−3, 3 × 10−6), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.

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