Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Henry R. Kranzler; Hang Zhou; Rachel L. Kember; Rachel Vickers Smith; Amy C. Justice; Scott Damrauer; Philip S. Tsao; Derek Klarin; Aris Baras; Jeffrey Reid; John Overton; Daniel J. Rader; Zhongshan Cheng; Janet P. Tate; William C. Becker; John Concato; Ke Xu; Renato Polimanti; Hongyu Zhao; Joel Gelernter

doi:10.1038/s41467-019-09480-8

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Henry R. Kranzler, Hang Zhou, Rachel L. Kember, Rachel Vickers Smith, Amy C. Justice, Scott Damrauer, Philip S. Tsao, Derek Klarin, Aris Baras, Jeffrey Reid, John Overton, Daniel J. Rader, Zhongshan Cheng, Janet P. Tate, William C. Becker, John Concato, Ke Xu, Renato Polimanti, Hongyu Zhao, Joel Gelernter

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

311 Scopus citations

Abstract

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.

Original language	English
Article number	1499
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-09480-8
State	Published - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019.

Funding

This research is based on data from the Million Veteran Program (MVP), Office of Research and Development, Veterans Health Administration, and was supported by award #I01BX003341. This publication does not represent the views of the Department of Veterans Affairs or the United States Government. A full acknowledgment of the MVP is included in Supplementary Note 1. We also appreciate access to summary data provided by the Psychiatric Genomics Consortium (PGC) Substance Use Disorders (SUD) working group. The PGC-SUD is supported by funds from NIDA and NIMH to MH109532 and, previously, had analyst support from NIAAA to U01AA008401 (COGA). PGC-SUD gratefully acknowledges its contributing studies and the participants in those studies without whom this effort would not be possible.

Funders	Funder number
Veterans Health Administration	01BX003341
National Institute of Mental Health	MH109532
National Institute of Mental Health
National Institute on Drug Abuse
National Institute on Alcohol Abuse and Alcoholism	U01AA008401
National Institute on Alcohol Abuse and Alcoholism
National Center for Advancing Translational Sciences (NCATS)	UL1TR001863
National Center for Advancing Translational Sciences (NCATS)
Biomedical Laboratory Research and Development, VA Office of Research and Development

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

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

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10.1038/s41467-019-09480-8

Cite this

Kranzler, H. R., Zhou, H., Kember, R. L., Vickers Smith, R., Justice, A. C., Damrauer, S., Tsao, P. S., Klarin, D., Baras, A., Reid, J., Overton, J., Rader, D. J., Cheng, Z., Tate, J. P., Becker, W. C., Concato, J., Xu, K., Polimanti, R., Zhao, H., & Gelernter, J. (2019). Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications, 10(1), Article 1499. https://doi.org/10.1038/s41467-019-09480-8

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abstract = "Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits{\textquoteright} PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.",

author = "Kranzler, {Henry R.} and Hang Zhou and Kember, {Rachel L.} and {Vickers Smith}, Rachel and Justice, {Amy C.} and Scott Damrauer and Tsao, {Philip S.} and Derek Klarin and Aris Baras and Jeffrey Reid and John Overton and Rader, {Daniel J.} and Zhongshan Cheng and Tate, {Janet P.} and Becker, {William C.} and John Concato and Ke Xu and Renato Polimanti and Hongyu Zhao and Joel Gelernter",

note = "Publisher Copyright: {\textcopyright} 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019.",

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Kranzler, HR, Zhou, H, Kember, RL, Vickers Smith, R, Justice, AC, Damrauer, S, Tsao, PS, Klarin, D, Baras, A, Reid, J, Overton, J, Rader, DJ, Cheng, Z, Tate, JP, Becker, WC, Concato, J, Xu, K, Polimanti, R, Zhao, H & Gelernter, J 2019, 'Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations', Nature Communications, vol. 10, no. 1, 1499. https://doi.org/10.1038/s41467-019-09480-8

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AU - Damrauer, Scott

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AU - Reid, Jeffrey

AU - Overton, John

AU - Rader, Daniel J.

AU - Cheng, Zhongshan

AU - Tate, Janet P.

AU - Becker, William C.

AU - Concato, John

AU - Xu, Ke

AU - Polimanti, Renato

AU - Zhao, Hongyu

AU - Gelernter, Joel

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Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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