| Title: | Genetic diversity fuels gene discovery for tobacco and alcohol use |
| Journal: | Nature |
| Published: | 7 Dec 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36477530/ |
| DOI: | https://doi.org/10.1038/s41586-022-05477-4 |
| URL: | https://www.nature.com/articles/s41586-022-05477-4.pdf |
Publication 10791
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Abstract
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.</p>
217 Authors
- Gretchen R. B. Saunders
- Xingyan Wang
- Fang Chen
- Seon-Kyeong Jang
- Mengzhen Liu
- Chen Wang
- Shuang Gao
- Yu Jiang
- Chachrit Khunsriraksakul
- Jacqueline M. Otto
- Clifton Addison
- Masato Akiyama
- Christine M. Albert
- Fazil Aliev
- Alvaro Alonso
- Donna K. Arnett
- Allison E. Ashley-Koch
- Aneel A. Ashrani
- Kathleen C. Barnes
- R. Graham Barr
- Traci M. Bartz
- Diane M. Becker
- Lawrence F. Bielak
- Emelia J. Benjamin
- Joshua C. Bis
- Gyda Bjornsdottir
- John Blangero
- Eugene R. Bleecker
- Jason D. Boardman
- Eric Boerwinkle
- Dorret I. Boomsma
- Meher Preethi Boorgula
- Donald W. Bowden
- Jennifer A. Brody
- Brian E. Cade
- Daniel I. Chasman
- Sameer Chavan
- Yii-Der Ida Chen
- Zhengming Chen
- Iona Cheng
- Michael H. Cho
- Hélène Choquet
- John W. Cole
- Marilyn C. Cornelis
- Francesco Cucca
- Joanne E. Curran
- Mariza de Andrade
- Danielle M. Dick
- Anna R. Docherty
- Ravindranath Duggirala
- Charles B. Eaton
- Marissa A. Ehringer
- Tõnu Esko
- Jessica D. Faul
- Lilian Fernandes Silva
- Edoardo Fiorillo
- Myriam Fornage
- Barry I. Freedman
- Maiken E. Gabrielsen
- Melanie E. Garrett
- Sina A. Gharib
- Christian Gieger
- Nathan Gillespie
- David C. Glahn
- Scott D. Gordon
- Charles C. Gu
- Dongfeng Gu
- Daniel F. Gudbjartsson
- Xiuqing Guo
- Jeffrey Haessler
- Michael E. Hall
- Toomas Haller
- Kathleen Mullan Harris
- Jiang He
- Pamela Herd
- John K. Hewitt
- Ian Hickie
- Bertha Hidalgo
- John E. Hokanson
- Christian Hopfer
- JoukeJan Hottenga
- Lifang Hou
- Hongyan Huang
- Yi-Jen Hung
- David J. Hunter
- Kristian Hveem
- Shih-Jen Hwang
- Chii-Min Hwu
- William Iacono
- Marguerite R. Irvin
- Yon Ho Jee
- Eric O. Johnson
- Yoonjung Y. Joo
- Eric Jorgenson
- Anne E. Justice
- Yoichiro Kamatani
- Robert C. Kaplan
- Jaakko Kaprio
- Sharon L. R. Kardia
- Matthew C. Keller
- Tanika N. Kelly
- Charles Kooperberg
- Tellervo Korhonen
- Peter Kraft
- Kenneth Krauter
- Johanna Kuusisto
- Markku Laakso
- Jessica Lasky-Su
- Wen-Jane Lee
- James J. Lee
- Daniel Levy
- Liming Li
- Kevin Li
- Yuqing Li
- Kuang Lin
- Penelope A. Lind
- Chunyu Liu
- Donald M. Lloyd-Jones
- Sharon M. Lutz
- Jiantao Ma
- Reedik Mägi
- Ani Manichaikul
- Nicholas G. Martin
- Ravi Mathur
- Nana Matoba
- Patrick F. McArdle
- Matt McGue
- Matthew B. McQueen
- Sarah E. Medland
- Andres Metspalu
- Deborah A. Meyers
- Iona Y. Millwood
- Braxton D. Mitchell
- Karen L. Mohlke
- Matthew Moll
- May E. Montasser
- Alanna C. Morrison
- Antonella Mulas
- Jonas B. Nielsen
- Kari E. North
- Elizabeth C. Oelsner
- Yukinori Okada
- Valeria Orrù
- Nicholette D. Palmer
- Teemu Palviainen
- Anita Pandit
- S. Lani Park
- Ulrike Peters
- Annette Peters
- Patricia A. Peyser
- Tinca J. C. Polderman
- Nicholas Rafaels
- Susan Redline
- Robert M. Reed
- Alex P. Reiner
- John P. Rice
- Stephen S. Rich
- Nicole E. Richmond
- Carol Roan
- Jerome I. Rotter
- Michael N. Rueschman
- Valgerdur Runarsdottir
- Nancy L. Saccone
- David A. Schwartz
- Aladdin H. Shadyab
- Jingchunzi Shi
- Suyash S. Shringarpure
- Kamil Sicinski
- Anne Heidi Skogholt
- Jennifer A. Smith
- Nicholas L. Smith
- Nona Sotoodehnia
- Michael C. Stallings
- Hreinn Stefansson
- Kari Stefansson
- Jerry A. Stitzel
- Xiao Sun
- Moin Syed
- Ruth Tal-Singer
- Amy E. Taylor
- Kent D. Taylor
- Marilyn J. Telen
- Khanh K. Thai
- Hemant Tiwari
- Constance Turman
- Thorarinn Tyrfingsson
- Tamara L. Wall
- Robin G. Walters
- David R. Weir
- Scott T. Weiss
- Wendy B. White
- John B. Whitfield
- Kerri L. Wiggins
- Gonneke Willemsen
- Cristen J. Willer
- Bendik S. Winsvold
- Huichun Xu
- Lisa R. Yanek
- Jie Yin
- Kristin L. Young
- Kendra A. Young
- Bing Yu
- Wei Zhao
- Wei Zhou
- Sebastian Zöllner
- Luisa Zuccolo
- Chiara Batini
- Andrew W. Bergen
- Laura J. Bierut
- Sean P. David
- Sarah A. Gagliano Taliun
- Dana B. Hancock
- Bibo Jiang
- Marcus R. Munafò
- Thorgeir E. Thorgeirsson
- 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