| Title: | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| Journal: | Nature Genetics |
| Published: | 14 Jan 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30643251/ |
| DOI: | https://doi.org/10.1038/s41588-018-0307-5 |
| URL: | https://europepmc.org/articles/pmc6358542?pdf=render |
Publication 2693
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Abstract
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.</p>
123 Authors
- Mengzhen Liu
- Yu Jiang
- Robbee Wedow
- Yue Li
- David M. Brazel
- Fang Chen
- Gargi Datta
- Jose Davila-Velderrain
- Daniel McGuire
- Chao Tian
- Xiaowei Zhan
- 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 Mägi
- 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 Stančáková
- 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
- Gonçalo Abecasis
- Dajiang J. Liu
- Scott Vrieze
1 Application
| Application ID | Title |
|---|---|
| 16651 | Genetic architecture of disease and related anthropometric phenotypes |
Enabling scientific discoveries that improve human health