Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
Name
nihms-1511852.pdf
Description
Accepted version
Size
1.46 MB
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Unknown
Checksum (MD5)
567b704fdde04743a6fe08363b644e8d
Author(s)
Li, Yue
Kellis, Manolis
Date Issued
2019
Journal
Nature Genetics
Publisher
Springer Nature
Version
Author's final manuscript
Abstract
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. 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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/s41588-018-0307-5
