Genome­-wide association study of alcohol consumption and genetic overlap with other health-­related traits in UK Biobank (=112,117)

T. K. Clarke, M. J. Adams, G. Davies, D. M. Howard, L. S. Hall, S. Padmanabhan, B. H. Smith, C. Hayward, D. J. Porteous, I. J. Deary, A. M. McIntosh

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Abstract

Alcohol consumption has been 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 low frequency. 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. We report significant genome-wide associations at 14 loci. 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 was 0.90 (S.E.=0.09, p-value = 7.16 x 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). 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.
Original languageEnglish
Pages (from-to)1376-1384
Number of pages9
JournalMolecular Psychiatry
Volume22
Issue number10
Early online date25 Jul 2017
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Genetics

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    Clarke, T. K., Adams, M. J., Davies, G., Howard, D. M., Hall, L. S., Padmanabhan, S., Smith, B. H., Hayward, C., Porteous, D. J., Deary, I. J., & McIntosh, A. M. (2017). Genome­-wide association study of alcohol consumption and genetic overlap with other health-­related traits in UK Biobank (=112,117). Molecular Psychiatry, 22(10), 1376-1384. https://doi.org/10.1038/mp.2017.153