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

23andMe Research Team, HUNT All-In Psychiatry, 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 FontanillasNicholas A. Furlotte, 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, Børge Sivertsen, Eystein Stordal, Gunnar Morken, Håvard Kallestad, Ingrid Heuch, John Anker Zwart, Katrine Kveli Fjukstad, Linda M. Pedersen, Maiken Elvestad Gabrielsen, Marianne Bakke Johnsen, Dajiang Liu

Research output: Contribution to journalLetter

35 Citations (Scopus)

Abstract

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . 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 (US)
Pages (from-to)237-244
Number of pages8
JournalNature Genetics
Volume51
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Tobacco Use
Alcohols
Tobacco Use Cessation
Genetic Association Studies
Synaptic Transmission
Sample Size
Smoking
Phenotype
Mortality
Health
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

23andMe Research Team ; HUNT All-In Psychiatry ; Liu, Mengzhen ; Jiang, Yu ; Wedow, Robbee ; Li, Yue ; Brazel, David M. ; Chen, Fang ; Datta, Gargi ; Davila-Velderrain, Jose ; McGuire, Daniel ; Tian, Chao ; Zhan, Xiaowei ; Agee, Michelle ; Alipanahi, Babak ; Auton, Adam ; Bell, Robert K. ; Bryc, Katarzyna ; Elson, Sarah L. ; Fontanillas, Pierre ; Furlotte, Nicholas A. ; Hinds, David A. ; Hromatka, Bethann S. ; Huber, Karen E. ; Kleinman, Aaron ; Litterman, Nadia K. ; McIntyre, Matthew H. ; Mountain, Joanna L. ; Northover, Carrie A.M. ; Sathirapongsasuti, J. Fah ; Sazonova, Olga V. ; Shelton, Janie F. ; Shringarpure, Suyash ; Tian, Chao ; Tung, Joyce Y. ; Vacic, Vladimir ; Wilson, Catherine H. ; Pitts, Steven J. ; Mitchell, Amy ; Skogholt, Anne Heidi ; Winsvold, Bendik S. ; Sivertsen, Børge ; Stordal, Eystein ; Morken, Gunnar ; Kallestad, Håvard ; Heuch, Ingrid ; Zwart, John Anker ; Fjukstad, Katrine Kveli ; Pedersen, Linda M. ; Gabrielsen, Maiken Elvestad ; Johnsen, Marianne Bakke ; Liu, Dajiang. / Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. In: Nature Genetics. 2019 ; Vol. 51, No. 2. pp. 237-244.
@article{9951a9ae2e9d43e1ade5fb7912744f49,
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 disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . 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 {HUNT All-In Psychiatry} 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 B{\o}rge Sivertsen and Eystein Stordal and Gunnar Morken and H{\aa}vard Kallestad and Ingrid Heuch and Zwart, {John Anker} and Fjukstad, {Katrine Kveli} and Pedersen, {Linda M.} and Gabrielsen, {Maiken Elvestad} and Johnsen, {Marianne Bakke} and Dajiang Liu",
year = "2019",
month = "2",
day = "1",
doi = "10.1038/s41588-018-0307-5",
language = "English (US)",
volume = "51",
pages = "237--244",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",

}

23andMe Research Team, HUNT All-In Psychiatry, Liu, M, Jiang, Y, Wedow, R, Li, Y, Brazel, DM, Chen, F, Datta, G, Davila-Velderrain, J, McGuire, D, Tian, C, Zhan, X, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, Hinds, DA, Hromatka, BS, Huber, KE, Kleinman, A, Litterman, NK, McIntyre, MH, Mountain, JL, Northover, CAM, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH, Pitts, SJ, Mitchell, A, Skogholt, AH, Winsvold, BS, Sivertsen, B, Stordal, E, Morken, G, Kallestad, H, Heuch, I, Zwart, JA, Fjukstad, KK, Pedersen, LM, Gabrielsen, ME, Johnsen, MB & Liu, D 2019, 'Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use', Nature Genetics, vol. 51, no. 2, pp. 237-244. https://doi.org/10.1038/s41588-018-0307-5

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. / 23andMe Research Team; HUNT All-In Psychiatry; Liu, Mengzhen; Jiang, Yu; Wedow, Robbee; Li, Yue; Brazel, David M.; Chen, Fang; Datta, Gargi; Davila-Velderrain, Jose; McGuire, Daniel; Tian, Chao; Zhan, Xiaowei; Agee, Michelle; Alipanahi, Babak; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna; Elson, Sarah L.; Fontanillas, Pierre; Furlotte, Nicholas A.; Hinds, David A.; Hromatka, Bethann S.; Huber, Karen E.; Kleinman, Aaron; Litterman, Nadia K.; McIntyre, Matthew H.; Mountain, Joanna L.; Northover, Carrie A.M.; Sathirapongsasuti, J. Fah; Sazonova, Olga V.; Shelton, Janie F.; Shringarpure, Suyash; Tian, Chao; Tung, Joyce Y.; Vacic, Vladimir; Wilson, Catherine H.; Pitts, Steven J.; Mitchell, Amy; Skogholt, Anne Heidi; Winsvold, Bendik S.; Sivertsen, Børge; Stordal, Eystein; Morken, Gunnar; Kallestad, Håvard; Heuch, Ingrid; Zwart, John Anker; Fjukstad, Katrine Kveli; Pedersen, Linda M.; Gabrielsen, Maiken Elvestad; Johnsen, Marianne Bakke; Liu, Dajiang.

In: Nature Genetics, Vol. 51, No. 2, 01.02.2019, p. 237-244.

Research output: Contribution to journalLetter

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 - HUNT All-In Psychiatry

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, Børge

AU - Stordal, Eystein

AU - Morken, Gunnar

AU - Kallestad, Håvard

AU - Heuch, Ingrid

AU - Zwart, John Anker

AU - Fjukstad, Katrine Kveli

AU - Pedersen, Linda M.

AU - Gabrielsen, Maiken Elvestad

AU - Johnsen, Marianne Bakke

AU - Liu, Dajiang

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . 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 disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . 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 - http://www.scopus.com/inward/record.url?scp=85060099159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060099159&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0307-5

DO - 10.1038/s41588-018-0307-5

M3 - Letter

C2 - 30643251

AN - SCOPUS:85060099159

VL - 51

SP - 237

EP - 244

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -