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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)

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 populati...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622124/
https://www.ncbi.nlm.nih.gov/pubmed/28937693
http://dx.doi.org/10.1038/mp.2017.153
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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
author_facet 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
author_sort Clarke, T-K
collection PubMed
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(−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.
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spelling pubmed-56221242017-10-02 Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117) 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 Mol Psychiatry Immediate Communication 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. Nature Publishing Group 2017-10 2017-07-25 /pmc/articles/PMC5622124/ /pubmed/28937693 http://dx.doi.org/10.1038/mp.2017.153 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Immediate Communication
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
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title_full Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title_fullStr Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title_full_unstemmed Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title_short Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
title_sort genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in uk biobank (n=112 117)
topic Immediate Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622124/
https://www.ncbi.nlm.nih.gov/pubmed/28937693
http://dx.doi.org/10.1038/mp.2017.153
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