| Title: |
Genetic diversity fuels gene discovery for tobacco and alcohol use |
| 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; Boorgula, Meher Preethi; Bowden, Donald W.; Brody, Jennifer A.; Cade, Brian E.; Chasman, Daniel; Chavan, Sameer; Chen, Yii-Der Ida; Chen, Zhengming; Cheng, Iona; Cho, Michael H.; Choquet, Helene; 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, Tonu; Faul, Jessica D.; Silva, Lilian Fernandes; Fiorillo, Edoardo; Fornage, Myriam; Freedman, Barry; 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, JoukeJan; 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; Magi, 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; Orru, 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; 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; Zollner, Sebastian; Zuccolo, Luisa; Project, The Biobank Japan; Batini, Chiara; Bergen, Andrew W.; Bierut, Laura J.; David, Sean P.; Taliun, Sarah A. Gagliano; Hancock, Dana B.; Jiang, Bibo; Munafo, Marcus R.; Thorgeirsson, Thorgeir E.; Liu, Dajiang J.; Vrieze, Scott |
| Contributors: |
Institute for Molecular Medicine Finland; University Management; Tellervo Korhonen / Principal Investigator; Genetic Epidemiology; University of Helsinki |
| Publisher Information: |
Nature Research |
| Publication Year: |
2023 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Neurotrophic factors; Disease; Prediction; Protein; Model; Biomedicine; Genetics; developmental biology; physiology |
| Description: |
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 injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). 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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://hdl.handle.net/10138/356325; 000934065100025 |
| Availability: |
https://hdl.handle.net/10138/356325 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.41ED27FB |
| Database: |
BASE |