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 Slagsvold
AU - Sivertsen, Børge
AU - Stordal, Eystein
AU - Morken, Gunnar
AU - Kallestad, Håvard
AU - Hottenga, Jouke Jan
AU - Jansen, Philip R.
AU - Willemsen, Gonneke
AU - Boomsma, Dorret I.
AU - Davies, Gareth E.
AU - Polderman, Tinca J.C.
AU - Posthuma, Danielle
AU - Heuch, Ingrid
AU - Zwart, John-Anker
AU - Fjukstad, Katrine Kveli
AU - Pedersen, Linda M.
AU - Gabrielsen, Maiken Elvestad
AU - Choquet, Hélène
AU - Docherty, Anna R
AU - Faul, Jessica D
AU - Foerster, Johanna R
AU - Fritsche, Lars G
AU - Gordon, Scott D
AU - Haessler, Jeffrey
AU - Huang, Hongyan
AU - Jang, Seon-Kyeong
AU - Ling, Yueh
AU - Mägi, Reedik
AU - Matoba, Nana
AU - McMahon, George
AU - Mulas, Antonella
AU - Orrù, Valeria
AU - Palviainen, Teemu
AU - Pandit, Anita
AU - Reginsson, Gunnar W
AU - Smith, Jennifer A
AU - Taylor, Amy E
AU - Turman, Constance
AU - Young, Hannah
AU - Young, Kendra A
AU - Zajac, Gregory J M
AU - Zhao, Wei
AU - Zhou, Wei
AU - Bjornsdottir, Gyda
AU - Boardman, Jason D
AU - Boehnke, Michael
AU - Chen, Chu
AU - Cucca, Francesco
AU - Eaton, Charles B
N1 - Funding Information: This study was designed and carried out by the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN). It was conducted by using the UK Biobank Resource under application number 16651. This study was supported by funding from US National Institutes of Health awards R01DA037904 to S.V., R01HG008983 to D. J. Liu., and R21DA040177 to D. J. Liu. Ethical review and approval was provided by the University of Minnesota institutional review board; all human subjects provided informed consent. A full list of acknowledgements is provided in the Supplementary Note. Publisher Copyright: © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
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.
KW - Alcohol Drinking/genetics
KW - Female
KW - Genetic Variation/genetics
KW - Genome-Wide Association Study/methods
KW - Humans
KW - Male
KW - Middle Aged
KW - Phenotype
KW - Risk
KW - Smoking/genetics
KW - Tobacco Use Disorder/genetics
KW - Tobacco/adverse effects
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 - https://doi.org/10.1038/s41588-018-0307-5
DO - https://doi.org/10.1038/s41588-018-0307-5
M3 - Article
C2 - 30643251
SN - 1061-4036
VL - 51
SP - 237
EP - 244
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -