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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Our study was supported by National Institute on Drug Abuse grants R01DA038632, R01DA047063, and R01DA047820.
The full summary-level association data from the meta-analysis for each of the smoking-related traits from this report are available through dbGaP accession number phs001672.v4.p1. 1000 Genomes Project reference panel can be downloaded from [ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/]. GWAS summary statistics used in the genetic correlation analysis were made publicly available by GSCAN, Social Science Genetic Association Consortium (SSGAC) [https://www.thessgac.org/data], and LD Hub.
Code to perform analyses in this paper is available from the authors upon request (B.L.), or from the URLs associated with each software in the online methods section.
Xu, Ke; Li, Boyang; McGinnis, Kathleen A.; Vickers-Smith, Rachel; Dao, Cecilia; Sun, Ning; Kember, Rachel L.; Zhou, Hang; Becker, William C.; Gelernter, Joel; Kranzler, Henry R.; Zhao, Hongyu; Justice, Amy C.; and VA Million Veteran Program, "Genome-Wide Association Study of Smoking Trajectory and Meta-Analysis of Smoking Status in 842,000 Individuals" (2020). Epidemiology Faculty Publications. 66.
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