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The power of genetic diversity in genome-wide association studies of lipids
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12 2021
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Source: Nature. 600(7890):675-679
Details:
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Alternative Title:Nature
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Personal Author:Graham, Sarah E ; Clarke, Shoa L ; Wu, Kuan-Han H ; Kanoni, Stavroula ; Zajac, Greg JM ; 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 ; Irvin, Marguerite R ; Oldmeadow, Christopher ; Kim, Han-Na ; Ryu, Seungho ; Timmers, Paul RHJ ; 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 WJ ; 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 LR ; 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 ; Chasman, Daniel I. ; Kaprio, Jaakko ; Pajukanta, Päivi ; Tusié-Luna, Teresa ; Aguilar-Salinas, Carlos A ; 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 ; Walker, Mark ; Koistinen, Heikki A ; Chandak, Giriraj R ; Yajnik, Chittaranjan S ; Mercader, Josep M ; Tusie-Luna, Teresa ; Aguilar-Salinas, Carlos ; 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 NA ; 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 ; Hart, Leen M t ; Elders, Petra JM ; Rader, Daniel J ; 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 ALM ; 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 KE ; Boomsma, Dorret I ; de Geus, Eco JC ; 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 ; Tsao, Phil 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 ; Boehnke, Michael ; Natarajan, Pradeep ; Peloso, Gina M ; Brown, Christopher D ; Morris, Andrew P ; Assimes, Themistocles L ; Deloukas, Panos ; Sun, Yan V ; Willer, Cristen J Less -
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Corporate Authors:
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Description: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.
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Pubmed ID:34887591
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Pubmed Central ID:PMC8730582
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Document Type:
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Funding:R01 DK093757/DK/NIDDK NIH HHSUnited States/ ; MC_UU_00006/1/MRC_/Medical Research CouncilUnited Kingdom/ ; I01 BX004821/BX/BLRD VAUnited States/ ; R01 HL109946/HL/NHLBI NIH HHSUnited States/ ; R01 HD030880/HD/NICHD NIH HHSUnited States/ ; ... More +R01 DK093757/DK/NIDDK NIH HHSUnited States/ ; MC_UU_00006/1/MRC_/Medical Research CouncilUnited Kingdom/ ; I01 BX004821/BX/BLRD VAUnited States/ ; R01 HL109946/HL/NHLBI NIH HHSUnited States/ ; R01 HD030880/HD/NICHD NIH HHSUnited States/ ; MC_UU_12026/2/MRC_/Medical Research CouncilUnited Kingdom/ ; R35 HL135824/HL/NHLBI NIH HHSUnited States/ ; MR/R024227/1/MRC_/Medical Research CouncilUnited Kingdom/ ; R35 HL135818/HL/NHLBI NIH HHSUnited States/ ; I01 BX003362/BX/BLRD VAUnited States/ ; R01 HG010297/HG/NHGRI NIH HHSUnited States/ ; U01 DP006266/DP/NCCDPHP CDC HHSUnited States/ ; 212946/Z/18/Z/WT_/Wellcome TrustUnited Kingdom/ ; MC_PC_19009/MRC_/Medical Research CouncilUnited Kingdom/ ; 212945/Z/18/Z/WT_/Wellcome TrustUnited Kingdom/ ; R01 HL153805/HL/NHLBI NIH HHSUnited States/ ; R01 DK072193/DK/NIDDK NIH HHSUnited States/ ; MC_PC_20026/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 AG017917/AG/NIA NIH HHSUnited States/ ; T32 HG000040/HG/NHGRI NIH HHSUnited States/ ; R01 HL127564/HL/NHLBI NIH HHSUnited States/ ; MC_PC_15018/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 DK062370/DK/NIDDK NIH HHSUnited States/ ; R01 HL105756/HL/NHLBI NIH HHSUnited States/ ; P30 AG010161/AG/NIA NIH HHSUnited States/ ; MC_UU_00017/1/MRC_/Medical Research CouncilUnited Kingdom/ ; IK2 CX001780/CX/CSRD VAUnited States/ ; MC_U137686851/MRC_/Medical Research CouncilUnited Kingdom/ ; RG/14/5/30893/BHF_/British Heart FoundationUnited Kingdom/ ; U01 HG011723/HG/NHGRI NIH HHSUnited States/ ; P30 DK020541/DK/NIDDK NIH HHSUnited States/ ; G9521010/MRC_/Medical Research CouncilUnited Kingdom/ ; MR/S011676/1/MRC_/Medical Research CouncilUnited Kingdom/ ; U19 AG063893/AG/NIA NIH HHSUnited States/ ; MC_UU_00007/10/MRC_/Medical Research CouncilUnited Kingdom/ ; U01 DK062370/DK/NIDDK NIH HHSUnited States/ ; R01 HL133218/HL/NHLBI NIH HHSUnited States/ ; G9815508/MRC_/Medical Research CouncilUnited Kingdom/ ; MC_PC_13049/MRC_/Medical Research CouncilUnited Kingdom/ ; P30 DK020572/DK/NIDDK NIH HHSUnited States/ ; R03 HL154284/HL/NHLBI NIH HHSUnited States/ ; MR/S019669/1/MRC_/Medical Research CouncilUnited Kingdom/ ; MC_PC_14135/MRC_/Medical Research CouncilUnited Kingdom/ ; 202802/Z/16/Z/WT_/Wellcome TrustUnited Kingdom/ ; 16896/CRUK_/Cancer Research UKUnited Kingdom/ ; R01 HL149683/HL/NHLBI NIH HHSUnited States/ ; R01 AG015819/AG/NIA NIH HHSUnited States/ ; K08 HG010155/HG/NHGRI NIH HHSUnited States/ ; K01 HL135405/HL/NHLBI NIH HHSUnited States/ Less -
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Volume:600
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Issue:7890
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Main Document Checksum:urn:sha256:bde9f11f8d6af307ac0164ffddbd880eba286c2f1f89787f29ff6bae6b20c435
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