Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
| Citation | . “Association Studies Of Up To 1.2 Million Individuals Yield New Insights Into The Genetic Etiology Of Tobacco And Alcohol Use.”. Nature Genetics, pp. 237-244. |
| Center | University of Michigan |
| Author | Mengzhen Liu, Yu Jiang, Robbee Wedow, Yue Li, David M Brazel, Fang Chen, Gargi Datta, Jose Davila-Velderrain, Daniel McGuire, Chao Tian, Xiaowei Zhan, 23andMe Research Team, HUNT All-In Psychiatry, Hélène Choquet, Anna R Docherty, Jessica D Faul, Johanna R Foerster, Lars G Fritsche, Maiken Elvestad Gabrielsen, Scott D Gordon, Jeffrey Haessler, Jouke-Jan Hottenga, Hongyan Huang, Seon-Kyeong Jang, Philip R Jansen, Yueh Ling, Reedik Magi, Nana Matoba, George McMahon, Antonella Mulas, Valeria Orrù, Teemu Palviainen, Anita Pandit, Gunnar W Reginsson, Anne Heidi Skogholt, Jennifer A Smith, Amy E Taylor, Constance Turman, Gonneke Willemsen, Hannah Young, Kendra A Young, Gregory J M Zajac, Wei Zhao, Wei Zhou, Gyda Bjornsdottir, Jason D Boardman, Michael Boehnke, Dorret I Boomsma, Chu Chen, Francesco Cucca, Gareth E Davies, Charles B Eaton, Marissa A Ehringer, Tõnu Esko, Edoardo Fiorillo, Nathan A Gillespie, Daniel F Gudbjartsson, Toomas Haller, Kathleen Mullan Harris, Andrew C Heath, John K Hewitt, Ian B Hickie, John E Hokanson, Christian J Hopfer, David J Hunter, William G Iacono, Eric O Johnson, Yoichiro Kamatani, Sharon L R Kardia, Matthew C Keller, Manolis Kellis, Charles Kooperberg, Peter Kraft, Kenneth S Krauter, Markku Laakso, Penelope A Lind, Anu Loukola, Sharon M Lutz, Pamela A F Madden, Nicholas G Martin, Matt McGue, Matthew B McQueen, Sarah E Medland, Andres Metspalu, Karen L Mohlke, Jonas B Nielsen, Yukinori Okada, Ulrike Peters, Tinca J C Polderman, Danielle Posthuma, Alexander P Reiner, John P Rice, Eric Rimm, Richard J Rose, Valgerdur Runarsdottir, Michael C Stallings, Alena Stancáková, Hreinn Stefansson, Khanh K Thai, Hilary A Tindle, Thorarinn Tyrfingsson, Tamara L Wall, David R Weir, Constance Weisner, John B Whitfield, Bendik Slagsvold Winsvold, Jie Yin, Luisa Zuccolo, Laura J Bierut, Kristian Hveem, James J Lee, Marcus R Munafò, Nancy L Saccone, Cristen J Willer, Marilyn C Cornelis, Sean P David, David A Hinds, Eric Jorgenson, Jaakko Kaprio, Jerry A Stitzel, Kari Stefansson, Thorgeir E Thorgeirsson, Goncalo Abecasis, Dajiang J Liu, Scott Vrieze |
| Abstract |
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. |
| Year of Publication |
2019
|
| Journal |
Nature genetics
|
| Volume |
51
|
| Issue |
2
|
| Number of Pages |
237-244
|
| Date Published |
12/2019
|
| ISSN Number |
1546-1718
|
| DOI |
10.1038/s41588-018-0307-5
|
| Alternate Journal |
Nat. Genet.
|
| PMID |
30643251
|
| PMCID |
PMC6358542
|
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