TY - JOUR
T1 - Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
JF - Nature Genetics
Y1 - 2019
A1 - Liu, Mengzhen
A1 - Jiang, Yu
A1 - Wedow, Robbee
A1 - Li, Yue
A1 - Brazel, David M
A1 - Chen, Fang
A1 - Datta, Gargi
A1 - Davila-Velderrain, Jose
A1 - McGuire, Daniel
A1 - Tian, Chao
A1 - Zhan, Xiaowei
A1 - Choquet, Hélène
A1 - Docherty, Anna R
A1 - Jessica Faul
A1 - Foerster, Johanna R
A1 - Fritsche, Lars G
A1 - Gabrielsen, Maiken Elvestad
A1 - Gordon, Scott D
A1 - Jeffrey Haessler
A1 - Jouke-Jan Hottenga
A1 - Huang, Hongyan
A1 - Jang, Seon-Kyeong
A1 - Philip R Jansen
A1 - Ling, Yueh
A1 - Mägi, Reedik
A1 - Matoba, Nana
A1 - McMahon, George
A1 - Mulas, Antonella
A1 - Orrù, Valeria
A1 - Palviainen, Teemu
A1 - Anita Pandit
A1 - Reginsson, Gunnar W
A1 - Skogholt, Anne Heidi
A1 - Smith, Jennifer A
A1 - Taylor, Amy E
A1 - Turman, Constance
A1 - Gonneke Willemsen
A1 - Young, Hannah
A1 - Young, Kendra A
A1 - Zajac, Gregory J M
A1 - Zhao, Wei
A1 - Zhou, Wei
A1 - Bjornsdottir, Gyda
A1 - Boardman, Jason D
A1 - Boehnke, Michael
A1 - Dorret I Boomsma
A1 - Chen, Chu
A1 - Francesco Cucca
A1 - Davies, Gareth E
A1 - Charles B Eaton
A1 - Ehringer, Marissa A
A1 - Tõnu Esko
A1 - Fiorillo, Edoardo
A1 - Gillespie, Nathan A
A1 - Gudbjartsson, Daniel F
A1 - Haller, Toomas
A1 - Kathleen Mullan Harris
A1 - Andrew C Heath
A1 - Hewitt, John K
A1 - Hickie, Ian B
A1 - Hokanson, John E
A1 - Hopfer, Christian J
A1 - Hunter, David J
A1 - Iacono, William G
A1 - Johnson, Eric O
A1 - Kamatani, Yoichiro
A1 - Sharon L R Kardia
A1 - Matthew C Keller
A1 - Kellis, Manolis
A1 - Charles Kooperberg
A1 - Kraft, Peter
A1 - Krauter, Kenneth S
A1 - Laakso, Markku
A1 - Penelope A Lind
A1 - Loukola, Anu
A1 - Lutz, Sharon M
A1 - Pamela A F Madden
A1 - Nicholas G Martin
A1 - McGue, Matt
A1 - Matthew B McQueen
A1 - Sarah E Medland
A1 - Andres Metspalu
A1 - Mohlke, Karen L
A1 - Nielsen, Jonas B
A1 - Okada, Yukinori
A1 - Peters, Ulrike
A1 - Tinca J Polderman
A1 - Posthuma, Danielle
A1 - Reiner, Alexander P
A1 - Rice, John P
A1 - Rimm, Eric
A1 - Rose, Richard J
A1 - Runarsdottir, Valgerdur
A1 - Stallings, Michael C
A1 - Stančáková, Alena
A1 - Stefansson, Hreinn
A1 - Thai, Khanh K
A1 - Hilary A Tindle
A1 - Tyrfingsson, Thorarinn
A1 - Wall, Tamara L
A1 - David R Weir
A1 - Weisner, Constance
A1 - Whitfield, John B
A1 - Winsvold, Bendik Slagsvold
A1 - Yin, Jie
A1 - Zuccolo, Luisa
A1 - Laura Bierut
A1 - Hveem, Kristian
A1 - Lee, James J
A1 - Munafò, Marcus R
A1 - Saccone, Nancy L
A1 - Willer, Cristen J
A1 - Marilyn C Cornelis
A1 - David, Sean P
A1 - Hinds, David A
A1 - Jorgenson, Eric
A1 - Kaprio, Jaakko
A1 - Stitzel, Jerry A
A1 - Stefansson, Kari
A1 - Thorgeirsson, Thorgeir E
A1 - Gonçalo R Abecasis
A1 - Liu, Dajiang J
A1 - Scott Vrieze
KW - Alcohol Drinking
KW - Female
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Middle Aged
KW - Phenotype
KW - Risk
KW - Smoking
KW - Tobacco
KW - Tobacco Use Disorder
AB - Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. 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.

VL - 51
IS - 2
ER -