GENOME-WIDE STUDY OF ALCOHOL CONSUMPTION AND THE GENETIC OVERLAP WITH HEALTH AND BEHAVIORAL TRAITS

Background Alcohol consumption is linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at lower frequencies. Methods We performed a Genome-Wide Association Study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. The SNP heritability of alcohol consumption was also investigated and the genetic correlation with health and behavioural traits. Results Thirteen genome-wide significant associations were detected. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption to be 0.90 (S.E.=0.09, p-value = 7.16 × 10–23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, S.E.=0.03), HDL cholesterol (rG=0.28, S.E.=0.05), smoking (rG=0.40, S.E.=0.06) and various anthropometric traits (e.g. Overweight, Rg=-0.19, S.E.=0.05). Discussion This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.