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

Ke Xu, Boyang Li, Kathleen A. McGinnis, Rachel Vickers-Smith, Cecilia Dao, Ning Sun, Rachel L. Kember, Hang Zhou, William C. Becker, Joel Gelernter, Henry R. Kranzler, Hongyu Zhao and Amy C. Justice ()
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Ke Xu: Yale School of Medicine
Boyang Li: VA Connecticut Healthcare System
Kathleen A. McGinnis: VA Connecticut Healthcare System
Rachel Vickers-Smith: University of Kentucky College of Public Health
Cecilia Dao: VA Connecticut Healthcare System
Ning Sun: Yale School of Public Health
Rachel L. Kember: University of Pennsylvania Perelman School of Medicine
Hang Zhou: Yale School of Medicine
William C. Becker: Yale School of Medicine
Joel Gelernter: Yale School of Medicine
Henry R. Kranzler: University of Pennsylvania Perelman School of Medicine
Hongyu Zhao: Yale School of Medicine
Amy C. Justice: Yale School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18489-3

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