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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)

Molecular psychiatry, 2017-10, Vol.22 (10), p.1376-1384 [Peer Reviewed Journal]

COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Oct 2017 ;Copyright © 2017 The Author(s) 2017 The Author(s) ;ISSN: 1359-4184 ;EISSN: 1476-5578 ;DOI: 10.1038/mp.2017.153 ;PMID: 28937693

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Title:
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
Author: 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 ; McIntosh, A M
Subjects: Adult ; Aged ; Alcohol dehydrogenase ; Alcohol Dehydrogenase - genetics ; Alcohol Dehydrogenase - metabolism ; Alcohol Drinking - genetics ; Alcohol use ; Alcoholism - genetics ; Alcohols ; Aldehyde dehydrogenase ; Aldehyde Dehydrogenase - genetics ; Anthropometry ; Biological Specimen Banks ; Body weight ; Cholesterol ; Dopamine D2 receptors ; Drinking (Alcoholic beverages) ; Female ; Genes ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; Genetic Testing ; Genetic Variation ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Heritability ; Humans ; Immediate Communication ; Klotho Proteins ; Male ; Membrane Proteins - genetics ; Middle Aged ; Nervous system ; Neurobiology ; Neurosciences ; Overweight ; Polymorphism, Single Nucleotide - genetics ; Single-nucleotide polymorphism ; Smoking ; Substance use ; United Kingdom ; Whites - genetics
Is Part Of: Molecular psychiatry, 2017-10, Vol.22 (10), p.1376-1384
Description: 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 ). 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: England: Nature Publishing Group
Language: English
Identifier: ISSN: 1359-4184
EISSN: 1476-5578
DOI: 10.1038/mp.2017.153
PMID: 28937693
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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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)

COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Oct 2017 ;Copyright © 2017 The Author(s) 2017 The Author(s) ;ISSN: 1359-4184 ;EISSN: 1476-5578 ;DOI: 10.1038/mp.2017.153 ;PMID: 28937693

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