Yale School of Medicine, New Haven, CT, 06511, USA.
VA Connecticut Healthcare System, West Haven, CT, 06516, USA.
Nat Commun. 2020 Oct 20;11(1):5302. doi: 10.1038/s41467-020-18489-3.
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 = 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.
在这里，我们报告了一项针对 286118 名百万退伍军人计划（MVP）参与者的纵向吸烟表型的全基因组关联研究（GWAS），在欧洲裔美国人中鉴定出了 18 个与当前吸烟与从不吸烟轨迹相关的位点，在非裔美国人中鉴定出了 1 个位点，在西班牙裔美国人中鉴定出了 1 个位点。功能注释优先考虑了几十个基因，其中显著的位点与表达数量性状基因座或染色质相互作用共定位。吸烟轨迹与 209 个复杂性状具有遗传相关性，其中 33 个性状吸烟是因果或结果因素。我们还对 MVP 中的吸烟状况进行了欧洲血统荟萃分析，以及对酒精和尼古丁使用的 GWAS 和测序联盟（GSCAN）（N=842717）进行了荟萃分析，鉴定出了 99 个吸烟起始的位点和 13 个吸烟终止的位点。总体而言，这项在多个群体中进行的大规模纵向吸烟表型全基因组关联研究，结合了吸烟状况的荟萃分析，为吸烟行为的遗传易感性提供了新的见解。
