Abstract
Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk.Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults.Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample.Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1 impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification.
Highlights
Alcohol use phenotypes are genetically influenced, with heritability for alcohol use disorder typically estimated at around 50% in twin and adoption studies (Heath et al, 1997; McGue, 1999; Prescott and Kendler, 1999; Verhulst et al, 2015)
Sex was included as a covariate in genetic analyses
In all but one of these bins the signal was limited to the African descent (AFR) group
Summary
Alcohol use phenotypes are genetically influenced, with heritability for alcohol use disorder typically estimated at around 50% in twin and adoption studies (Heath et al, 1997; McGue, 1999; Prescott and Kendler, 1999; Verhulst et al, 2015). Other alcohol-related phenotypes, such as initiation of use, typical consumption, maximum number of drinks consumed in a day, or initial response to alcohol, are modestly to moderately heritable (Fowler et al, 2007; Poelen et al, 2009; Agrawal et al, 2011; Kalu et al, 2012). As these measures constitute steps along the trajectory to alcohol problems among some individuals, elucidating their genetic etiology is important. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk
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