Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans.

Abstract

We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24-hour period ("MaxDrinks"), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). The samples included our GWAS samples (Yale-UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. The results confirmed significant associations of the well-known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p=5.96×10(-15) ) and AAs (rs2066702 Arg370Cys, p=2.50×10(-10) ). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale-UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00×10(-8) ) and rs2309169 close to ANKRD36 on chromosome 2 (p=5.58×10(-9) ). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p=1.99×10(-7) ) and rs2309169 remained highly significant (2.12×10(-9) ). The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.