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

Clarke, T.-K. et al. (2017) Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117). Molecular Psychiatry, 22(10), pp. 1376-1384. (doi: 10.1038/mp.2017.153) (PMID:28937693) (PMCID:PMC5622124)

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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, for example, ALDH2 and 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 single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two 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 analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 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), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Authors: Clarke, T.-K., Adams, M.J., Davies, G., Howard, D.M., Hall, L.S., Padmanabhan, S., Murray, A.D., Smith, B.H., Campbell, A., Hayward, C., Porteous, D.J., Deary, I.J., and McIntosh, A.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Psychiatry
Publisher:Nature Publishing Group
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:25 July 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Molecular Psychiatry 22(10):1376-1384
Publisher Policy:Reproduced under a Creative Commons License

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