Association Studies of up to 1.2 Million Individuals Yield New Insights into the Genetic Etiology of Tobacco and Alcohol Use

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Citation

Liu, Mengzhen; Jiang, Yu; Wedow, Robbee; Li, Yue; Brazel, David M.; Chen, Fang; Datta, Gargi; Davila-Velderrain, Jose; McGuire, Daniel; & Tian, Chao, et al. (2019). Association Studies of up to 1.2 Million Individuals Yield New Insights into the Genetic Etiology of Tobacco and Alcohol Use. Nature Genetics, 51, 237-244. PMCID: PMC6358542

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.

URL

http://dx.doi.org/10.1038/s41588-018-0307-5

Reference Type

Journal Article

Year Published

2019

Journal Title

Nature Genetics

Author(s)

Liu, Mengzhen
Jiang, Yu
Wedow, Robbee
Li, Yue
Brazel, David M.
Chen, Fang
Datta, Gargi
Davila-Velderrain, Jose
McGuire, Daniel
Tian, Chao
Zhan, Xiaowei
23andMe Research Team,
HUNT All-In Psychiatry,
Choquet, Helene
Docherty, Anna R.
Faul, Jessica D.
Foerster, Johanna R.
Fritsche, Lars G.
Gabrielsen, Maiken Elvestad
Gordon, Scott D.
Haessler, Jeffrey
Hottenga, Jouke-Jan
Huang, Hongyan
Jang, Seon-Kyeong
Jansen, Philip R.
Ling, Yueh
Magi, Reedik
Matoba, Nana
McMahon, George
Mulas, Antonella
Orru, Valeria
Palviainen, Teemu
Pandit, Anita
Reginsson, Gunnar W.
Skogholt, Anne Heidi
Smith, Jennifer A.
Taylor, Amy E.
Turman, Constance
Willemsen, Gonneke
Young, Hannah
Young, Kendra A.
Zajac, Gregory J. M.
Zhao, Wei
Zhou, Wei
Bjornsdottir, Gyda
Boardman, Jason D.
Boehnke, Michael
Boomsma, Dorret I.
Chen, Chu
Cucca, Francesco
Davies, Gareth E.
Eaton, Charles B.
Ehringer, Marissa A.
Esko, Tonu
Fiorillo, Edoardo
Gillespie, Nathan A.
Gudbjartsson, Daniel F.
Haller, Toomas
Harris, Kathleen Mullan
Heath, Andrew C.
Hewitt, John K.
Hickie, Ian B.
Hokanson, John E.
Hopfer, Christian J.
Hunter, David J.
Iacono, William G.
Johnson, Eric O.
Kamatani, Yoichiro
Kardia, Sharon L. R.
Keller, Matthew C.
Kellis, Manolis
Kooperberg, Charles L.
Kraft, Peter
Krauter, Kenneth S.
Laakso, Markku
Lind, Penelope A.
Loukola, Anu
Lutz, Sharon M.
Madden, Pamela A. F.
Martin, Nicholas G.
McGue, Matt
McQueen, Matthew B.
Medland, Sarah E.
Metspalu, Andres
Mohlke, Karen L.
Nielsen, Jonas B.
Okada, Yukinori
Peters, Ulrike
Polderman, Tinca J. C.
Posthuma, Danielle
Reiner, Alexander P.
Rice, John P.
Rimm, Eric B.
Rose, Richard J.
Runarsdottir, Valgerdur
Stallings, Michael C.
Stancakova, Alena
Stefansson, Hreinn
Thai, Khanh K.
Tindle, Hilary A.
Tyrfingsson, Thorarinn
Wall, Tamara L.
Weir, David R.
Weisner, Constance
Whitfield, John B.
Winsvold, Bendik Slagsvold
Yin, Jie
Zuccolo, Luisa
Bierut, Laura J.
Hveem, Kristian
Lee, James J.
Munafò, Marcus
Saccone, Nancy L.
Willer, Cristen J.
Cornelis, Marilyn C.
David, Sean P.
Hinds, David A.
Jorgenson, Eric
Kaprio, Jaakko
Stitzel, Jerry A.
Stefansson, Kari
Thorgeirsson, Thorgeir E.
Abecasis, Gonçalo R.
Liu, Dajiang J.
Vrieze, Scott

PMCID

PMC6358542

ORCiD

Harris, KM - 0000-0001-9757-1026