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 - 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 - Heuch, Ingrid
AU - Zwart, John Anker
AU - Fjukstad, Katrine Kveli
AU - Pedersen, Linda M.
AU - Gabrielsen, Maiken Elvestad
AU - Johnsen, Marianne Bakke
AU - Skrove, Marit
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/1/14
Y1 - 2019/1/14
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/pages/publications/85060099159
U2 - 10.1038/s41588-018-0307-5
DO - 10.1038/s41588-018-0307-5
M3 - Letter
C2 - 30643251
AN - SCOPUS:85060099159
SN - 1061-4036
VL - 51
SP - 237
EP - 244
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -