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

23andMe Research team, 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 & 31 others David A. Hinds, Bethann 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

Research output: Contribution to journalArticleAcademicpeer-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.
LanguageEnglish
JournalNature Genetics
DOIs
Publication statusE-pub ahead of print - 2019

Cite this

@article{d6127763905e44ae88b1ab80a1e7e269,
title = "Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use",
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.",
author = "{23andMe Research team} and Mengzhen Liu and Yu Jiang and Robbee Wedow and Yue Li and Brazel, {David M.} and Fang Chen and Gargi Datta and Jose Davila-Velderrain and Daniel McGuire and Chao Tian and Xiaowei Zhan and Michelle Agee and Babak Alipanahi and Adam Auton and Bell, {Robert K.} and Katarzyna Bryc and Elson, {Sarah L.} and Pierre Fontanillas and Furlotte, {Nicholas A.} and Hinds, {David A.} and Hromatka, {Bethann S.} and Huber, {Karen E.} and Aaron Kleinman and Litterman, {Nadia K.} and McIntyre, {Matthew H.} and Mountain, {Joanna L.} and Northover, {Carrie A. M.} and Sathirapongsasuti, {J. Fah} and Sazonova, {Olga V.} and Shelton, {Janie F.} and Suyash Shringarpure and Chao Tian and Tung, {Joyce Y.} and Vladimir Vacic and Wilson, {Catherine H.} and Pitts, {Steven J.} and Amy Mitchell and Skogholt, {Anne Heidi} and Winsvold, {Bendik S.} and Sivertsen, {B. rge} and Eystein Stordal and Gunnar Morken and Kallestad, {H. vard} and Ingrid Heuch and John-Anker Zwart and Fjukstad, {Katrine Kveli} and Pedersen, {Linda M.} and Gabrielsen, {Maiken Elvestad} and Jansen, {Philip R.} and Danielle Posthuma",
year = "2019",
doi = "10.1038/s41588-018-0307-5",
language = "English",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",

}

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. / 23andMe Research team.

In: Nature Genetics, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

AU - 23andMe Research team

AU - Liu, Mengzhen

AU - Jiang, Yu

AU - Wedow, Robbee

AU - Li, Yue

AU - Brazel, David M.

AU - Chen, Fang

AU - Datta, Gargi

AU - Davila-Velderrain, Jose

AU - McGuire, Daniel

AU - Tian, Chao

AU - Zhan, Xiaowei

AU - Agee, Michelle

AU - Alipanahi, Babak

AU - Auton, Adam

AU - Bell, Robert K.

AU - Bryc, Katarzyna

AU - Elson, Sarah L.

AU - Fontanillas, Pierre

AU - Furlotte, Nicholas A.

AU - Hinds, David A.

AU - Hromatka, Bethann S.

AU - Huber, Karen E.

AU - Kleinman, Aaron

AU - Litterman, Nadia K.

AU - McIntyre, Matthew H.

AU - Mountain, Joanna L.

AU - Northover, Carrie A. M.

AU - Sathirapongsasuti, J. Fah

AU - Sazonova, Olga V.

AU - Shelton, Janie F.

AU - Shringarpure, Suyash

AU - Tian, Chao

AU - Tung, Joyce Y.

AU - Vacic, Vladimir

AU - Wilson, Catherine H.

AU - Pitts, Steven J.

AU - Mitchell, Amy

AU - Skogholt, Anne Heidi

AU - Winsvold, Bendik S.

AU - Sivertsen, B. rge

AU - Stordal, Eystein

AU - Morken, Gunnar

AU - Kallestad, H. vard

AU - Heuch, Ingrid

AU - Zwart, John-Anker

AU - Fjukstad, Katrine Kveli

AU - Pedersen, Linda M.

AU - Gabrielsen, Maiken Elvestad

AU - Jansen, Philip R.

AU - Posthuma, Danielle

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060099159&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30643251

U2 - 10.1038/s41588-018-0307-5

DO - 10.1038/s41588-018-0307-5

M3 - Article

JO - Nature Genetics

T2 - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -