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Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
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Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
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Journal Article
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
2017
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/43
/ 631/208
/ Adult
/ Aged
/ Alcohol Dehydrogenase - genetics
/ Alcohol Dehydrogenase - metabolism
/ Aldehyde Dehydrogenase - genetics
/ Drinking (Alcoholic beverages)
/ Female
/ Genes
/ Genetic Predisposition to Disease - genetics
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Male
/ Medicine
/ Membrane Proteins - genetics
/ Polymorphism, Single Nucleotide - genetics
/ Single-nucleotide polymorphism
/ Smoking
