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Genetic diversity fuels gene discovery for tobacco and alcohol use

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 Eur...

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Autores principales: 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., Fernandes Silva, Lilian, 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, 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, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771818/
https://www.ncbi.nlm.nih.gov/pubmed/36477530
http://dx.doi.org/10.1038/s41586-022-05477-4
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author 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.
Fernandes Silva, Lilian
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, 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
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
author_facet 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.
Fernandes Silva, Lilian
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, 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
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
author_sort Saunders, Gretchen R. B.
collection PubMed
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.
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spelling pubmed-97718182022-12-23 Genetic diversity fuels gene discovery for tobacco and alcohol use 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. Fernandes Silva, Lilian 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, 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 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 Nature Article 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. Nature Publishing Group UK 2022-12-07 2022 /pmc/articles/PMC9771818/ /pubmed/36477530 http://dx.doi.org/10.1038/s41586-022-05477-4 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
Fernandes Silva, Lilian
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, JoukeJan
Hou, Lifang
Huang, Hongyan
Hung, Yi-Jen
Hunter, David J.
Hveem, Kristian
Hwang, Shih-Jen
Hwu, Chii-Min
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David, Sean P.
Gagliano Taliun, Sarah A.
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Jiang, Bibo
Munafò, Marcus R.
Thorgeirsson, Thorgeir E.
Liu, Dajiang J.
Vrieze, Scott
Genetic diversity fuels gene discovery for tobacco and alcohol use
title Genetic diversity fuels gene discovery for tobacco and alcohol use
title_full Genetic diversity fuels gene discovery for tobacco and alcohol use
title_fullStr Genetic diversity fuels gene discovery for tobacco and alcohol use
title_full_unstemmed Genetic diversity fuels gene discovery for tobacco and alcohol use
title_short Genetic diversity fuels gene discovery for tobacco and alcohol use
title_sort genetic diversity fuels gene discovery for tobacco and alcohol use
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771818/
https://www.ncbi.nlm.nih.gov/pubmed/36477530
http://dx.doi.org/10.1038/s41586-022-05477-4
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