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

doi:10.1038/mp.2017.153

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

Dentistry

Research output: Contribution to journal › Article › peer-review

280 Citations (Scopus)

288 Downloads (Pure)

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 language	English
Pages (from-to)	1376-1384
Number of pages	9
Journal	Molecular Psychiatry
Volume	22
Issue number	10
Early online date	25 Jul 2017
DOIs	https://doi.org/10.1038/mp.2017.153
Publication status	Published - Oct 2017

Keywords

Genetics

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/mp.2017.153Licence: CC BY

Final Published Version
© The Author(s) 2017. 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/
Final published version, 859 KBLicence: CC BY

Cite this

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 (N =112,117). Molecular Psychiatry, 22(10), 1376-1384. https://doi.org/10.1038/mp.2017.153

@article{e45b80a2d4bc49d28900d42fd7c4e5d5,

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

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.",

keywords = "Genetics",

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

note = "Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK GWAS alcohol consumption and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z). We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged.",

year = "2017",

month = oct,

doi = "10.1038/mp.2017.153",

language = "English",

volume = "22",

pages = "1376--1384",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "10",

}

Clarke, TK, Adams, MJ, Davies, G, Howard, DM, Hall, LS, Padmanabhan, S, Smith, BH, Hayward, C, Porteous, DJ, Deary, IJ & McIntosh, AM 2017, 'Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N =112,117)', Molecular Psychiatry, vol. 22, no. 10, pp. 1376-1384. https://doi.org/10.1038/mp.2017.153

TY - JOUR

T1 - Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N =112,117)

AU - Clarke, T. K.

AU - Adams, M. J.

AU - Davies, G.

AU - Howard, D. M.

AU - Hall, L. S.

AU - Padmanabhan, S.

AU - Smith, B. H.

AU - Hayward, C.

AU - Porteous, D. J.

AU - Deary, I. J.

AU - McIntosh, A. M.

N1 - Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK GWAS alcohol consumption and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z). We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged.

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Genetics

U2 - 10.1038/mp.2017.153

DO - 10.1038/mp.2017.153

M3 - Article

C2 - 28937693

AN - SCOPUS:85036511638

SN - 1359-4184

VL - 22

SP - 1376

EP - 1384

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

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