Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals

doi:10.1038/s41467-020-18489-3

Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals

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Abstract

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (N_total = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.

Original language	English
Article number	5302
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18489-3
State	Published - Dec 1 2020

Bibliographical note

Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Funding

This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by award #MVP004. This publication does not represent the views of the Department of Veterans Affairs or the United States Government. Our study was supported by National Institute on Drug Abuse grants R01DA038632, R01DA047063, and R01DA047820. We thank all participants in the MVP who allowed access to their electronic health records and provided blood samples for genomic analyses. We thank all authors and consortia for making their summary statistics publicly available to the research community.

Funders	Funder number
Million Veteran Program Science Meeting
Veterans Health Administration
National Institutes of Health (NIH)	1I01BX003341
National Institutes of Health (NIH)
National Institute on Drug Abuse	R01DA047820, R01DA042691, R01DA038632, R01DA047063
National Institute on Drug Abuse
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

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10.1038/s41467-020-18489-3

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title = "Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals",

abstract = "Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.",

author = "Ke Xu and Boyang Li and McGinnis, {Kathleen A.} and Rachel Vickers-Smith and Cecilia Dao and Ning Sun and Kember, {Rachel L.} and Hang Zhou and Becker, {William C.} and Joel Gelernter and Kranzler, {Henry R.} and Hongyu Zhao and Justice, {Amy C.}",

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AU - Xu, Ke

AU - Li, Boyang

AU - McGinnis, Kathleen A.

AU - Vickers-Smith, Rachel

AU - Dao, Cecilia

AU - Sun, Ning

AU - Kember, Rachel L.

AU - Zhou, Hang

AU - Becker, William C.

AU - Gelernter, Joel

AU - Kranzler, Henry R.

AU - Zhao, Hongyu

AU - Justice, Amy C.

PY - 2020/12/1

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N2 - Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.

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Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals

Abstract

Bibliographical note

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ASJC Scopus subject areas

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