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oai:recercat.cat:2072/4629822026-03-13T10:22:14Zcom_2072_98col_2072_378192

The power of genetic diversity in genome-wide association studies of lipids Graham, Sarah E. Chang, Kyong-Mi Cho, Kelly O'Donnell, Christopher J. Gaziano, John M. Wilson, Peter Rotimi, Charles Hazelhurst, Scott Ramsay, Michele Trembath, Richard C. van Heel, David A. Tamiya, Gen Yamamoto, Masayuki Kim, Bong-Jo Mohlke, Karen L. Frayling, Timothy M. Hirschhorn, Joel N. Kathiresan, Sekar Boehnke, Michael Natarajan, Pradeep Peloso, Gina M. Brown, Christopher D. Morris, Andrew P. Assimes, Themistocles Deloukas, Panos Sun, Yan V. Willer, Cristen J. Clarke, Shoa L. Wu, Kuan-Han H. Kanoni, Stavroula Zajac, Greg J. M. Ramdas, Shweta Surakka, Ida Ntalla, Ioanna Vedantam, Sailaja Winkler, Thomas W. Locke, Adam E. Marouli, Eirini Hwang, Mi Yeong Han, Sohee Narita, Akira Choudhury, Ananyo Bentley, Amy R. Ekoru, Kenneth Verma, Anurag Trivedi, Bhavi Martin, Hilary C. Hunt, Karen A. Hui, Qin Klarin, Derek Zhu, Xiang Thorleifsson, Gudmar Helgadottir, Anna Gudbjartsson, Daniel F. Holm, Hilma Olafsson, Isleifur Akiyama, Masato Sakaue, Saori Terao, Chikashi Kanai, Masahiro Zhou, Wei Brumpton, Ben M. Rasheed, Humaira Ruotsalainen, Sanni E. Havulinna, Aki S. Veturi, Yogasudha Feng, QiPing Rosenthal, Elisabeth A. Lingren, Todd Pacheco, Jennifer Allen Pendergrass, Sarah A. Haessler, Jeffrey Giulianini, Franco Bradford, Yuki Miller, Jason E. Campbell, Archie Lin, Kuang Millwood, Iona Y. Hindy, George Rasheed, Asif Faul, Jessica D. Zhao, Wei Weir, David R. Turman, Constance Huang, Hongyan Graff, Mariaelisa Mahajan, Anubha Brown, Michael R. Zhang, Weihua Yu, Ketian Schmidt, Ellen M. Pandit, Anita Gustafsson, S. Yin, Xianyong Luan, Jian'an Zhao, Jing-Hua Matsuda, Fumihiko Jang, Hye-Mi Yoon, Kyungheon Medina-Gomez, Carolina Pitsillides, Achilleas Hottenga, Jouke Jan Willemsen, Gonneke Wood, Andrew R. Ji, Yingji Gao, Zishan Haworth, Simon Mitchell, Ruth E. Chai, Jin-Fang Aadahl, Mette Yao, Jie Manichaikul, Ani Warren, Helen R. Ramírez, Julia Bork-Jensen, Jette Kårhus, Line L. Goel, Anuj Sabater-Lleal, Maria Noordam, Raymond Sidore, Carlo Fiorillo, Edoardo McDaid, Aaron F. Marques-Vidal, Pedro Wielscher, Matthias Trompet, Stella Sattar, Naveed Møllehave, Line Tang Thuesen, Betina H. Munz, Matthias Zeng, Lingyao Huang, Jianfeng Yang, Bin Poveda, Alaitz Kurbasic, Azra Lamina, Claudia Forer, Lukas Scholz, Markus Galesloot, Tessel E. Bradfield, Jonathan Paul Daw, E. Warwick Zmuda, Joseph M. Mitchell, Jonathan S. Fuchsberger, Christian Christensen, Henry Brody, Jennifer A. Feitosa, Mary Wojczynski, Mary K. Preuss, Michael Mangino, Massimo Christofidou, Paraskevi Verweij, Niek Benjamins, Jan W. Engmann, Jorgen Kember, Rachel L. Slieker, Roderick C. Lo, Ken Sin Zilhao, N. R. Le, Phuong Kleber, Marcus E. Delgado, Graciela E. Huo, Shsofeng Ikeda, Daisuke D. Iha, Hiroyuki Yang, Jian Liu, Jun Leonard, Hampton L. Marten, Jonathan Schmidt, Börge Arendt, Marina Smyth, Laura J. Cañadas-Garre, Marisa Wang, Chaolong Nakatochi, Masahiro Wong, Andrew Hutri-Kähönen, Nina Sim, Xueling Xia, Rui Huerta-Chagoya, Alicia Fernandez-Lopez, Juan Carlos Lyssenko, Valeriya Ahmed, Meraj Jackson, Anne U. Irvin, Marguerite R. Oldmeadow, Christopher Kim, Han-Na Ryu, Seungho Timmers, Paul R. H. J. Arbeeva, Liubov Dorajoo, Rajkumar Lange, Leslie A. Chai, Xiaoran Prasad, Gauri Lorés-Motta, Laura Pauper, Marc Long, Jirong Li, Xiaohui Theusch, Elizabeth Takeuchi, Fumihiko Spracklen, Cassandra N. Loukola, Anu-Maria Bollepalli, Sailalitha Warner, Sophie C. Wang, Ya Xing Wei, Wen B. Nutile, Teresa Ruggiero, Daniela Sung, Yun Ju Hung, Yi-Jen Chen, Shufeng Liu, Fangchao Yang, Jingyun Kentistou, Katherine A. Gorski, Mathias Brumat, Marco Meidtner, Karina Bielak, Lawrence F. Smith, Jennifer A. Hebbar, Prashantha Farmaki, Aliki-Eleni Hofer, Edith Lin, Maoxuan Xue, Chao Zhang, Jifeng Concas, Maria Pina Vaccargiu, Simona van der Most, Peter J. Pitkänen, Niina Cade, Brian E. Lee, Jiwon van der Laan, Sander W. Chitrala, Kumaraswamy Naidu Weiss, Stefan Zimmermann, Martina E. Lee, Jong Young Choi, Hyeok Sun Nethander, Maria Freitag-Wolf, Sandra Southam, Lorraine Rayner, Nigel W. Wang, Carol A. Lin, Shih Yi Wang, Jun-Sing Couture, Christian Lyytikäinen, Leo-Pekka Nikus, Kjell Cuellar-Partida, Gabriel Vestergaard, Henrik Hildalgo, Bertha Giannakopoulou, Olga Cai, Qiuyin Obura, Morgan O. van Setten, Jessica Li, Xiaoyin Schwander, Karen Terzikhan, Natalie Shin, Jae Hun Jackson, Rebecca D. Reiner, Alewxander P. Martin, Lisa W. Chen, Zhengming Li, Liming Highland, Heather M. Young, Kristin L. Kawaguchi, Takahisa Thiery, Joachim Bis, Joshua C. Nadkarni, Girish N. Launer, Lenore Joy Li, Huaixing Nalls, Mike A. Raitakari, Olli T. Ichihara, Sahoko Wild, Sarah Nelson, Christopher P. Campbell, Harry Jäger, Susanne Nabika, Toru Al-Mulla, Fahd Niinikoski, Harri Braund, Peter S. Kolcic, Ivana Kovacs, Peter Giardoglou, Tota Katsuya, Tomohiro Bhatti, Konain Fatima de Kleijn, Dominique de Borst, Gert J. Kim, Eung Kweon Adams, Hieab H. H. Ikram, M. Arfan Zhu, X. Asselbergs, Folkert W. Kraaijeveld, Adriaan O. Beulens, Joline W. J. Shu, Xiao-Ou Rallidis, Loukianos S. Pedersen, Oluf Hansen, Torben Mitchell, Paul Hewitt, Alex W. Kähönen, Mika Pérusse, Louis Bouchard, Claude Tönjes, Anke Chen, Yii Der Ida Pennell, Craig E. Mori, Trevor A. Lieb, Wolfgang Franke, Andre Ohlsson, Claes Mellström, Dan Cho, Yoon Shin Lee, Hyejin Yuan, Jan-Min Koh, Woon-Puay Rhee, Sang Youl Woo, Jeong-Taek Heid, Iris M. Stark, Klaus J. Völzke, Henry Homuth, Georg Evans, Michele K. Zonderman, Alan B. Polasek, Ozren Pasterkamp, Gerard Hoefer, Imo E. Redline, Susan Pahkala, Katja Oldehinkel, Albertine J. Snieder, Harold Biino, Ginevra Schmidt, Reinhold Schmidt, Helena Chen, Y. Eugene Bandinelli, Stefania Dedoussis, George Thanaraj, Thangavel Alphonse Kardia, Sharon L. R. Kato, Norihiro Schulze, Matthias B. Girotto, Giorgia Jung, Bettina Böger, Carsten A. Joshi, Peter K. Bennett, David A. De Jager, Philip L. Lu, Xiangfeng Mamakou, Vasiliki Brown, Morris Caulfield, Mark Munroe, Patricia B. Guo, Xiuqing Ciullo, Marina Jonas, Jost B. Samani, Nilesh J. Kaprio, Jaakko Pajukanta, Päivi Adair, Linda S. Bechayda, Sonny Augustin de Silva, H. Janaka Wickremasinghe, Ananda R. Krauss, Ronald M. Wu, Jer-Yuarn Zheng, Wei den Hollander, Anneke I. Bharadwaj, Dwaipayan Correa, Adolfo Wilson, James G. Lind, Lars Heng, Chew-Kiat Nelson, Amanda E. Golightly, Yvonne M. Wilson, James F. Penninx, Brenda WJH. Kim, Hyung-Lae Attia, John Scott, Rodney J. Rao, D. C. Arnett, Donna Walker, Mark Koistinen, Heikki A. Chandak, Giriraj Ratan Yajnik, Chittaranjan S. Mercader, Josep M. Tusié-Luna, Teresa Aguilar-Salinas, Carlos Alberto Gonzalez Villalpando, Clicerio Orozco, Lorena Fornage, Myriam Tai, E. Shyong van Dam, Rob M. Lehtimäki, Terho Chaturvedi, Nish Yokota, Mitsuhiro Liu, Junfeng Reilly, Dermot F. McKnight, Amy Jayne Kee, Frank Jöckel, Karl-Heinz McCarthy, Mark I. Palmer, Colin N. A. Vitart, Veronique Hayward, Caroline Simonsick, Eleanor van Duijn, Cornelia M. Lu, Fan Qu, Jia Hishigaki, Haretsugu Lin, Xu März, Winfried Parra, Esteban J. Cruz, Miguel Gudnason, Vilmundur Tardif, Jean-Claude Lettre, Guillaume 't Hart, Leen M. Elders, Petra J. M. Damrauer, Scott M. Kumari, Meena Kivimaki, Mika van der Harst, Pim Spector, Tim Loos, Ruth J. F. Province, Michael A. Psaty, Bruce M. Brandslund, Ivan Pramstaller, Peter P. Christensen, Kaare Ripatti, Samuli Widén, Elisabeth Hakonarson, Hakon Grant, Struan F. A. Kiemeney, Lambertus A. L. M. de Graaf, Jacqueline Loeffler, Markus Kronenberg, Florian Gu, Dongfeng Erdmann, Jeanette Schunkert, Heribert Franks, Paul W. Linneberg, Allan Jukema, J. Wouter Khera, Amit V. Männikkö, Minna Jarvelin, Marjo-Riitta Kutalik, Zoltan Cucca, Francesco Mook-Kanamori, Dennis O. van Dijk, Ko Willems Watkins, Hugh Strachan, David P. Grarup, Niels Sever, Peter Poulter, Neil Rotter, Jerome I. Dantoft, Thomas M. Karpe, Fredrik Neville, Matt J. Timpson, Nicholas J. Cheng, Ching-Yu Wong, Tien-Yin Khor, Chiea Chuen Sabanayagam, Charumathi Peters, Annette Gieger, Christian Hattersley, A. T. Pedersen, Nancy L. Magnusson, Patrik K. E. Boomsma, Dorret I. de Geus, Eco J. C. Cupples, L. Adrienne van Meurs, Joyce B. J. Ghanbari, Mohsen Gordon-Larsen, Penny Huang, Wei Kim, Young Jin Tabara, Yasuharu Wareham, Nicholas J. Langenberg, Claudia Zeggini, Eleftheria Kuusisto, Johanna Laakso, Markku Ingelsson, Erik Abecasis, Goncalo Chambers, John C. Kooner, Jaspal S. de Vries, Paul S. Morrison, Alanna North, Kari E. Daviglus, Martha Kraft, Peter Martin, Nicholas G. Whitfield, John B. Abbas, Shahid Saleheen, Danish Walters, Robin G. Holmes, Michael V. Black, Corri Smith, Blair H. Justice, Anne E. Baras, Aris Buring, Julie E. Ridker, Paul M. Chasman, Daniel I. Kooperberg, Charles Wei, Wei-Qi Jarvik, Gail P. Namjou, Bahram Hayes, M. Geoffrey Ritchie, Marylyn D. Jousilahti, Pekka Salomaa, Veikko Hveem, Kristian Åsvold, Bjørn Olav Kubo, Michiaki Kamatani, Yoichiro Okada, Yukinori Murakami, Yoshinori Thorsteinsdottir, Unnur Stefánsson, Kári Ho, Yuk-Lam Lynch, Julie A. Rader, Daniel J. Tsao, Philip S. Cardiovascular Diseases Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Multifactorial Inheritance Polymorphism, Single Nucleotide Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine, we anticipate that increased diversity of participants will lead to more accurate and equitable application of polygenic scores in clinical practice. 2021 Article https://ddd.uab.cat/record/264450 urn:10.1038/s41586-021-04064-3 urn:oai:ddd.uab.cat:264450 urn:scopus_id:85121605114 urn:articleid:14764687v600n7890p675 urn:pmid:34887591 urn:pmc-uid:8730582 urn:pmcid:PMC8730582 urn:oai:pubmedcentral.nih.gov:8730582 eng Nature ; Vol. 600 Núm. 7890 (12 2021), p. 675-679 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. https://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf