Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Mengzhen Liu, Yu Jiang, Robbee Wedow, Yue Li, David M. Brazel, Fang Chen, Gargi Datta, Jose Davila-Velderrain, Daniel McGuire, Chao Tian, Xiaowei Zhan, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, David A. HindsBethann S. Hromatka, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Carrie A. M. Northover, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Steven J. Pitts, Amy Mitchell, Anne Heidi Skogholt, Bendik S. Winsvold, B. rge Sivertsen, Eystein Stordal, Gunnar Morken, H. vard Kallestad, Ingrid Heuch, John-Anker Zwart, Katrine Kveli Fjukstad, Linda M. Pedersen, Maiken Elvestad Gabrielsen, Philip R. Jansen, Danielle Posthuma, 23andMe Research team, Eric Jorgenson, Jerry A. Stitzel, Dajiang J. Liu, Scott Vrieze

Research output: Contribution to journalLetterAcademicpeer-review

Abstract

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6–11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.
Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalNature Genetics
Volume51
Issue number2
Early online date2019
DOIs
Publication statusPublished - 1 Feb 2019

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