Genetic Contributors to Variation in Alcohol Consumption Vary by Race/Ethnicity in a Large Multi-Ethnic Genome-wide Association Study

Abstract

Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. While a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic Whites, Hispanic/Latinos, East Asians, and African Americans. We examined two statistically independent phenotypes reflecting subjects’ alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status), and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously-reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (OR=0.40, p=2.28×10 ⁻⁷²) in East Asians, and also an effect on drinks/week (beta=−0.17, p=5.42×10 ⁻⁴) in the same group. We also observed a genome-wide significant association in non-Hispanic Whites between the previously-reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, p=2.47×10 ⁻²⁰ for drinker status and beta=−0.19, p=1.91×10 ⁻³⁵ for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, p=4.35×10 ⁻⁷ and beta=−0.21, p=2.58×10 ⁻⁶, respectively). While prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=−0.04, p=3.41×10 ⁻¹⁰ for drinks/week and OR=0.96, p=4.08×10 ⁻⁵ for drinker status), and rs4665985 (beta = 0.04, p=2.26×10 ⁻⁸ for drinks/week and OR=1.04, p=5.00×10 ⁻⁴ for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1, and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.