Refereed journal article or data article (A1)

The power of genetic diversity in genome-wide association studies of lipids




List of AuthorsGraham Sarah E., 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 Stefan, 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., Ramirez 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 T., 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 P., Daw E. Warwick, Zmuda Joseph M., Mitchell Jonathan S., Fuchsberger Christian, Christensen Henry, Brody Jennifer A., Feitosa Mary F., 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 Nuno R., Le Phuong, Kleber Marcus E., Delgado Graciela E., Huo Shaofeng, 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., Yousri Noha A., 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, 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 Alexander P., Martin Lisa Warsinger, Chen Zhengming, Li Liming, Highland Heather M., Young Kristin L., Kawaguchi Takahisa, Thiery Joachim, Bis Joshua C., Nadkarni Girish N., Launer Lenore J., Li Huaixing, Nalls Mike A., Raitakari Olli T., Ichihara Sahoko, Wild Sarah H., 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 Xiaofeng, 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 Jian-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 J., 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, Kim Hyung-Lae, Attia John, Scott Rodney J., Rao D. C., Arnett Donna K., Hunt Steven C., Walker Mark, Koistinen Heikki A., Chandak Giriraj R., Yajnik Chittaranjan S., Mercader Josep M., Tusié-Luna Teresa, Aguilar-Salinas Carlos A., Villalpando Clicerio Gonzalez, Orozco Lorena, Fornage Myriam, Tai E. Shyong, van Dam Rob M., Lehtimäki Terho, Chaturvedi Nish, Yokota Mitsuhiro, Liu Jianjun, 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 D., 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 Andrew 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 C., 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, Stefansson Kari, Ho Yuk-Lam, Lynch Julie A., Rader Daniel J., Tsao Philip S., Chang Kyong-Mi, Cho Kelly, O’Donnell Christopher J., Gaziano John M., Wilson Peter, Rotimi Charles N., Hazelhurst Scott, Ramsay Michèle, 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, VA Million Veteran Program, Global Lipids Genetics Consortium, Boehnke Michael, Natarajan Pradeep, Peloso Gina M., Brown Christopher D., Morris Andrew P., Assimes Themistocles L., Deloukas Panos, Sun Yan V., Willer Cristen J.

PublisherSpringer Nature

Publication year2021

JournalNature

Volume number600

Issue number7890

Start page675

End page679

eISSN1476-4687

DOIhttp://dx.doi.org/10.1038/s41586-021-04064-3


Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. 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 GWAS4-23 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 patterns24. 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 medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.


Last updated on 2023-13-09 at 11:27