Full Citation

Title: Genetic diversity fuels gene discovery for tobacco and alcohol use

Citation Type: Journal Article

Publication Year: 2022

ISBN:

ISSN: 1476-4687

DOI: 10.1038/s41586-022-05477-4

NSFID:

PMCID:

PMID: 36477530

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. A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Url: https://www.nature.com/articles/s41586-022-05477-4

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Authors: Saunders, Gretchen R.B.; Wang, Xingyan; Chen, Fang; Jang, Seon Kyeong; Liu, Mengzhen; Wang, Chen; Gao, Shuang; Jiang, Yu; Khunsriraksakul, Chachrit; Otto, Jacqueline M.; Addison, Clifton; Akiyama, Masato; Albert, Christine M.; Aliev, Fazil; Alonso, Alvaro; Arnett, Donna K.; Ashley-Koch, Allison E.; Ashrani, Aneel A.; Barnes, Kathleen C.; Barr, R. Graham; Bartz, Traci M.; Becker, Diane M.; Bielak, Lawrence F.; Benjamin, Emelia J.; Bis, Joshua C.; Bjornsdottir, Gyda; Blangero, John; Bleecker, Eugene R.; Boardman, Jason D.; Boerwinkle, Eric; Boomsma, Dorret I.; Boorgula, Meher Preethi; Bowden, Donald W.; Brody, Jennifer A.; Cade, Brian E.; Chasman, Daniel I.; Chavan, Sameer; Chen, Yii Der Ida; Chen, Zhengming; Cheng, Iona; Cho, Michael H.; Choquet, Hélène; Cole, John W.; Cornelis, Marilyn C.; Cucca, Francesco; Curran, Joanne E.; de Andrade, Mariza; Dick, Danielle M.; Docherty, Anna R.; Duggirala, Ravindranath; Eaton, Charles B.; Ehringer, Marissa A.; Esko, Tõnu; Faul, Jessica D.; Silva, Lilian Fernandes; Fiorillo, Edoardo; Fornage, Myriam; Freedman, Barry I.; Gabrielsen, Maiken E.; Garrett, Melanie E.; Gharib, Sina A.; Gieger, Christian; Gillespie, Nathan; Glahn, David C.; Gordon, Scott D.; Gu, Charles C.; Gu, Dongfeng; Gudbjartsson, Daniel F.; Guo, Xiuqing; Haessler, Jeffrey; Hall, Michael E.; Haller, Toomas; Harris, Kathleen Mullan; He, Jiang; Herd, Pamela; Hewitt, John K.; Hickie, Ian; Hidalgo, Bertha; Hokanson, John E.; Hopfer, Christian; Hottenga, Jouke Jan; Hou, Lifang; Huang, Hongyan; Hung, Yi Jen; Hunter, David J.; Hveem, Kristian; Hwang, Shih Jen; Hwu, Chii Min; Iacono, William; Irvin, Marguerite R.; Jee, Yon Ho; Johnson, Eric O.; Joo, Yoonjung Y.; Jorgenson, Eric; Justice, Anne E.; Kamatani, Yoichiro; Kaplan, Robert C.; Kaprio, Jaakko; Kardia, Sharon L.R.; Keller, Matthew C.; Kelly, Tanika N.; Kooperberg, Charles; Korhonen, Tellervo; Kraft, Peter; Krauter, Kenneth; Kuusisto, Johanna; Laakso, Markku; Lasky-Su, Jessica; Lee, Wen Jane; Lee, James J.; Levy, Daniel; Li, Liming; Li, Kevin; Li, Yuqing; Lin, Kuang; Lind, Penelope A.; Liu, Chunyu; Lloyd-Jones, Donald M.; Lutz, Sharon M.; Ma, Jiantao; Mägi, Reedik; Manichaikul, Ani; Martin, Nicholas G.; Mathur, Ravi; Matoba, Nana; McArdle, Patrick F.; McGue, Matt; McQueen, Matthew B.; Medland, Sarah E.; Metspalu, Andres; Meyers, Deborah A.; Millwood, Iona Y.; Mitchell, Braxton D.; Mohlke, Karen L.; Moll, Matthew; Montasser, May E.; Morrison, Alanna C.; Mulas, Antonella; Nielsen, Jonas B.; North, Kari E.; Oelsner, Elizabeth C.; Okada, Yukinori; Orrù, Valeria; Palmer, Nicholette D.; Palviainen, Teemu; Pandit, Anita; Park, S. Lani; Peters, Ulrike; Peters, Annette; Peyser, Patricia A.; Polderman, Tinca J.C.; Rafaels, Nicholas; Redline, Susan; Reed, Robert M.; Reiner, Alex P.; Rice, John P.; Rich, Stephen S.; Richmond, Nicole E.; Roan, Carol; Rotter, Jerome I.; Rueschman, Michael N.; Runarsdottir, Valgerdur; Saccone, Nancy L.; Schwartz, David A.; Shadyab, Aladdin H.; Shi, Jingchunzi; Shringarpure, Suyash S.; Sicinski, Kamil; Skogholt, Anne Heidi; Smith, Jennifer A.; Smith, Nicholas L.; Sotoodehnia, Nona; Stallings, Michael C.; Stefansson, Hreinn; Stefansson, Kari; Stitzel, Jerry A.; Sun, Xiao; Syed, Moin; Tal-Singer, Ruth; Taylor, Amy E.; Taylor, Kent D.; Telen, Marilyn J.; Thai, Khanh K.; Tiwari, Hemant; Turman, Constance; Tyrfingsson, Thorarinn; Wall, Tamara L.; Walters, Robin G.; Weir, David R.; Weiss, Scott T.; White, Wendy B.; Whitfield, John B.; Wiggins, Kerri L.; Willemsen, Gonneke; Willer, Cristen J.; Winsvold, Bendik S.; Xu, Huichun; Yanek, Lisa R.; Yin, Jie; Young, Kristin L.; Young, Kendra A.; Yu, Bing; Zhao, Wei; Zhou, Wei; Zöllner, Sebastian; Zuccolo, Luisa; Batini, Chiara; Bergen, Andrew W.; Bierut, Laura J.; David, Sean P.; Gagliano Taliun, Sarah A.; Hancock, Dana B.; Jiang, Bibo; Munafò, Marcus R.; Thorgeirsson, Thorgeir E.; Liu, Dajiang J.; Vrieze, Scott

Periodical (Full): Nature 2022 612:7941

Issue: 7941

Volume: 612

Pages: 720-724

Countries: