Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples

Emma C. Johnson; Sandra Sanchez-Roige; Laura Acion; Mark J. Adams; Kathleen K. Bucholz; Grace Chan; Michael J. Chao; David B. Chorlian; Danielle M. Dick; Howard J. Edenberg; Tatiana Foroud; Caroline Hayward; Jon Heron; Victor Hesselbrock; Matthew Hickman; Kenneth S. Kendler; Sivan Kinreich; John Kramer; Sally I-Chun Kuo; Samuel Kuperman; Dongbing Lai; Andrew M. McIntosh; Jacquelyn L. Meyers; Martin H. Plawecki; Bernice Porjesz; David Porteous; Marc A. Schuckit; Jinni Su; Yong Zang; Abraham A. Palmer; Arpana Agrawal; Toni-Kim Clarke; Alexis C. Edwards

doi:10.1017/S0033291719004045

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Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples

Journal article

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Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples

Emma C. Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J. Adams, Kathleen K. Bucholz, Grace Chan, Michael J. Chao, David B. Chorlian, Danielle M. Dick, Howard J. Edenberg, …

Psychological medicine, Vol.51(7), pp.1147-1156

05/01/2021

DOI: 10.1017/S0033291719004045

PMCID: PMC7405725

PMID: 31955720

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https://www.research.ed.ac.uk/en/publications/d2f27a9c-9181-455d-95b9-33eb716c70e4View

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Abstract

Background Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds. Methods We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes. Results In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R-2 = 0.47-0.68%, p = 2.0 x 10(-8)-1.0 x 10(-10)), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 x 10(-8)); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R-2 = 0.96%, p = 4.8 x 10(-6)). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R-2 = 0.27%, p = 5.5 x 10(-11)), while AUDIT-P PRS was more associated with problem drinking (R-2 = 0.40%, p = 9.0 x 10(-7)). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R-2 = 0.18%, p < 2.0 x 10(-16)). Conclusions AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

Life Sciences & Biomedicine

Psychiatry

Psychology

Psychology, Clinical

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Social Sciences

Details

Title: Subtitle: Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
Creators: Emma C. Johnson - Washington University in St. Louis
Sandra Sanchez-Roige - Department of Psychiatry
Laura Acion - University of Iowa
Mark J. Adams - University of Edinburgh
Kathleen K. Bucholz - Washington University in St. Louis
Grace Chan - University of Connecticut
Michael J. Chao - Icahn School of Medicine at Mount Sinai
David B. Chorlian - SUNY Downstate Health Sciences University
Danielle M. Dick - Virginia Commonwealth University
Howard J. Edenberg - Indiana University
Tatiana Foroud - Indiana University
Caroline Hayward - University of Edinburgh
Jon Heron - University of Bristol
Victor Hesselbrock - University of Connecticut
Matthew Hickman - University of Bristol
Kenneth S. Kendler - Virginia Commonwealth University
Sivan Kinreich - SUNY Downstate Health Sciences University
John Kramer - University of Iowa
Sally I-Chun Kuo - Virginia Commonwealth University
Samuel Kuperman - University of Iowa
Dongbing Lai - Indiana University
Andrew M. McIntosh - University of Edinburgh
Jacquelyn L. Meyers - SUNY Downstate Health Sciences University
Martin H. Plawecki - Indiana University
Bernice Porjesz - SUNY Downstate Health Sciences University
David Porteous - University of Edinburgh
Marc A. Schuckit - Department of Psychiatry
Jinni Su - Arizona State University
Yong Zang - Indiana University
Abraham A. Palmer - University of California San Diego
Arpana Agrawal - Washington University in St. Louis
Toni-Kim Clarke - University of Edinburgh
Alexis C. Edwards - Virginia Commonwealth University
Resource Type: Journal article
Publication Details: Psychological medicine, Vol.51(7), pp.1147-1156
DOI: 10.1017/S0033291719004045
PMID: 31955720
PMCID: PMC7405725
NLM abbreviation: Psychol Med
ISSN: 0033-2917
eISSN: 1469-8978
Publisher: Cambridge Univ Press
Number of pages: 10
Grant note: G0800612 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Pfizer Sackler Foundation Janssen; Johnson & Johnson; Johnson & Johnson USA; Janssen Biotech Inc Eli Lilly
Language: English
Date published: 05/01/2021
Academic Unit: Psychiatry
Record Identifier: 9984293655702771

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