The power of genetic diversity in genome-wide association studies of lipids
Creators: name: Bork-Jensen, Jette
name: Hirschhorn, Joel N.
name: Kutalik, Zoltan
name: Ruotsalainen, Sanni E.
name: Ruggiero, Daniela
name: Hebbar, Prashantha
name: Adams, Hieab H. H.
name: Kähönen, Mika
name: Han, Sohee
name: Bhatti, Konain Fatima
name: Yang, Bin
name: Locke, Adam E.
name: Millwood, Iona Y.
name: Giannakopoulou, Olga
name: van der Harst, Pim
name: Schunkert, Heribert
name: Aguilar-Salinas, Carlos A.
name: Mitchell, Jonathan S.
name: Correa, Adolfo
name: Freitag-Wolf, Sandra
name: Gudnason, Vilmundur
name: Sun, Yan V.
name: Verweij, Niek
name: Brown, Morris
name: Xia, Rui
name: Kember, Rachel L.
name: Mori, Trevor A.
name: Launer, Lenore J.
name: Yoon, Kyungheon
name: Jung, Bettina
name: Chai, Jin Fang
name: Thorsteinsdottir, Unnur
name: Ji, Yingji
name: Cai, Qiuyin
name: Chen, Y. Eugene
name: Pendergrass, Sarah A.
name: Polasek, Ozren
name: Terzikhan, Natalie
name: Theusch, Elizabeth
name: Kronenberg, Florian
name: Rhee, Sang Youl
name: Gordon-Larsen, Penny
name: Haessler, Jeffrey
name: Smith, Jennifer A.
name: Palmer, Colin N. A.
name: Zhu, Xiaofeng
name: Nutile, Teresa
name: Pasterkamp, Gerard
name: Dorajoo, Rajkumar
name: de Silva, H. Janaka
name: Lu, Xiangfeng
name: Walker, Mark
name: Kraft, Peter
name: Neville, Matt J.
name: Surakka, Ida
name: Cañadas-Garre, Marisa
name: Liu, Jun
name: Huang, Jianfeng
name: Giardoglou, Tota
name: Lehtimäki, Terho
name: Bandinelli, Stefania
name: Hazelhurst, Scott
name: Guo, Xiuqing
name: Holm, Hilma
name: Christensen, Henry
name: Vedantam, Sailaja
name: Lyssenko, Valeriya
name: Lind, Lars
name: Reiner, Alexander P.
name: Natarajan, Pradeep
name: Penninx, Brenda
name: Jang, Hye-Mi
name: Murakami, Yoshinori
name: Choi, Hyeok Sun
name: Chai, Xiaoran
name: van Setten, Jessica
name: Åsvold, Bjørn Olav
name: Liu, Jianjun
name: Schwander, Karen
name: Wang, Chaolong
name: Liu, Fangchao
name: Graff, Mariaelisa
name: Girotto, Giorgia
name: Lyytikäinen, Leo-Pekka
name: Kim, Hyung-Lae
name: Black, Corri
name: Chambers, John C.
name: Stark, Klaus J.
name: Ghanbari, Mohsen
name: Ciullo, Marina
name: Chitrala, Kumaraswamy Naidu
name: Kårhus, Line L.
name: Kleber, Marcus E.
name: Le, Phuong
name: Kathiresan, Sekar
name: Wong, Tien-Yin
name: Havulinna, Aki S.
name: Ichihara, Sahoko
name: Hwang, Mi Yeong
name: Pahkala, Katja
name: Yang, Jingyun
name: Willemsen, Gonneke
name: Sung, Yun Ju
name: Farmaki, Aliki-Eleni
name: de Kleijn, Dominique
name: Völzke, Henry
name: Wu, Jer-Yuarn
name: Lin, Xu
name: McCarthy, Mark I.
name: Verma, Anurag
name: Pramstaller, Peter P.
name: Hindy, George
name: Chasman, Daniel I.
name: Cho, Yoon Shin
name: Willer, Cristen J.
name: Fuchsberger, Christian
name: Franks, Paul W.
name: Shu, Xiao-Ou
name: Bradfield, Jonathan P.
name: Mitchell, Paul
name: Trompet, Stella
name: Feng, QiPing
name: Adair, Linda S.
name: Southam, Lorraine
name: Stefansson, Kari
name: Hattersley, Andrew T.
name: Vaccargiu, Simona
name: Wong, Andrew
name: Huerta-Chagoya, Alicia
name: Nelson, Christopher P.
name: Qu, Jia
name: Aadahl, Mette
name: Medina-Gomez, Carolina
name: van Dijk, Ko Willems
name: Benjamins, Jan W.
name: Gao, Zishan
name: Bis, Joshua C.
name: Shin, Jae Hun
name: Samani, Nilesh J.
name: Bollepalli, Sailalitha
name: Woo, Jeong-Taek
name: Møllehave, Line T.
name: Giulianini, Franco
name: Cho, Kelly
name: Haworth, Simon
name: Huang, Wei
name: de Vries, Paul S.
name: Asselbergs, Folkert W.
name: Hoefer, Imo E.
name: Kiemeney, Lambertus A. L. M.
name: Ohlsson, Claes
name: Pedersen, Nancy L.
name: Long, Jirong
name: Noordam, Raymond
name: Hayes, M. Geoffrey
name: Chaturvedi, Nish
name: Wickremasinghe, Ananda R.
name: Zhao, Wei
name: Poulter, Neil
name: Cheng, Ching-Yu
name: Jukema, J. Wouter
name: Brody, Jennifer A.
name: Katsuya, Tomohiro
name: Yin, Xianyong
name: Dedoussis, George
name: Iha, Hiroyuki
name: Ripatti, Samuli
name: Whitfield, John B.
name: Bradford, Yuki
name: O’Donnell, Christopher J.
name: Ahmed, Meraj
name: Martin, Lisa Warsinger
name: Schmidt, Reinhold
name: Kraaijeveld, Adriaan O.
name: Rotter, Jerome I.
name: Scholz, Markus
name: Simonsick, Eleanor
name: Kubo, Michiaki
name: Braund, Peter S.
name: Hui, Qin
name: Boomsma, Dorret I.
name: Oldmeadow, Christopher
name: Manichaikul, Ani
name: Reilly, Dermot F.
name: Kim, Bong-Jo
name: Nakatochi, Masahiro
name: Chen, Zhengming
name: Spector, Tim D.
name: Villalpando, Clicerio Gonzalez
name: Brown, Christopher D.
name: Cuellar-Partida, Gabriel
name: Veturi, Yogasudha
name: Kooner, Jaspal S.
name: Weiss, Stefan
name: Walters, Robin G.
name: Zheng, Wei
name: März, Winfried
name: Hofer, Edith
name: de Borst, Gert J.
name: Pandit, Anita
name: Trivedi, Bhavi
name: Christensen, Kaare
name: Rasheed, Asif
name: Sattar, Naveed
name: Kooperberg, Charles
name: Daw, E. Warwick
name: Rosenthal, Elisabeth A.
name: Bechayda, Sonny Augustin
name: Takeuchi, Fumihiko
name: Ho, Yuk-Lam
name: ’t Hart, Leen M.
name: Martin, Hilary C.
name: Lange, Leslie A.
name: Jackson, Rebecca D.
name: Lee, Hyejin
name: van der Most, Peter J.
name: Hutri-Kähönen, Nina
name: Ryu, Seungho
name: Pitsillides, Achilleas
name: Engmann, Jorgen
name: Yao, Jie
name: Watkins, Hugh
name: Tamiya, Gen
name: Nadkarni, Girish N.
name: Vitart, Veronique
name: Terao, Chikashi
name: Brumat, Marco
name: Kaprio, Jaakko
name: Graham, Sarah E.
name: Ramdas, Shweta
name: Warner, Sophie C.
name: Hveem, Kristian
name: Psaty, Bruce M.
name: Thuesen, Betina H.
name: Fornage, Myriam
name: Rao, D. C.
name: Morrison, Alanna C.
name: Jäger, Susanne
name: Kim, Young Jin
name: Elders, Petra J. M.
name: Sidore, Carlo
name: Heng, Chew-Kiat
name: Helgadottir, Anna
name: Mellström, Dan
name: Peloso, Gina M.
name: de Graaf, Jacqueline
name: Magnusson, Patrik K. E.
name: Krauss, Ronald M.
name: Bennett, David A.
name: Khera, Amit V.
name: Feitosa, Mary F.
name: Pérusse, Louis
name: Choudhury, Ananyo
name: Arendt, Marina
name: Luan, Jian’an
name: Thanaraj, Thangavel Alphonse
name: Lin, Shih-Yi
name: Widén, Elisabeth
name: Poveda, Alaitz
name: Jarvik, Gail P.
name: Gaziano, John M.
name: Caulfield, Mark J.
name: Mahajan, Anubha
name: Cade, Brian E.
name: Smith, Blair H.
name: Grarup, Niels
name: Dantoft, Thomas M.
name: Galesloot, Tessel E.
name: Lieb, Wolfgang
name: Brumpton, Ben M.
name: Kolcic, Ivana
name: Laakso, Markku
name: de Geus, Eco J. C.
name: Kamatani, Yoichiro
name: Zimmermann, Martina E.
name: Warren, Helen R.
name: Slieker, Roderick C.
name: Kim, Han-Na
name: Mohlke, Karen L.
name: Li, Huaixing
name: Khor, Chiea Chuen
name: Vestergaard, Henrik
name: Orozco, Lorena
name: Loos, Ruth J. F.
name: Bouchard, Claude
name: Hung, Yi-Jen
name: Huo, Shaofeng
name: Gu, Dongfeng
name: Langenberg, Claudia
name: Kanoni, Stavroula
name: McDaid, Aaron F.
name: Province, Michael A.
name: Frayling, Timothy M.
name: Assimes, Themistocles L.
name: Nalls, Mike A.
name: Campbell, Harry
name: Gustafsson, Stefan
name: Lin, Kuang
name: Koistinen, Heikki A.
name: Wei, Wei-Qi
name: Buring, Julie E.
name: Leonard, Hampton L.
name: Zmuda, Joseph M.
name: Spracklen, Cassandra N.
name: Marten, Jonathan
name: Young, Kristin L.
name: Zhang, Weihua
name: Yuan, Jian-Min
name: Kanai, Masahiro
name: Mamakou, Vasiliki
name: Timmers, Paul R. H. J.
name: Pitkänen, Niina
name: Sim, Xueling
name: Olafsson, Isleifur
name: Zhang, Jifeng
name: Prasad, Gauri
name: Strachan, David P.
name: Pennell, Craig E.
name: Yamamoto, Masayuki
name: Wood, Andrew R.
name: Wu, Kuan-Han H.
name: Zonderman, Alan B.
name: Meidtner, Karina
name: Peters, Annette
name: Ntalla, Ioanna
name: Koh, Woon-Puay
name: Brandslund, Ivan
name: Akiyama, Masato
name: Loeffler, Markus
name: Tai, E. Shyong
name: Nikus, Kjell
name: Damrauer, Scott M.
name: Fiorillo, Edoardo
name: Chandak, Giriraj R.
name: Attia, John
name: Jonas, Jost B.
name: Ikram, M. Arfan
name: Kurbasic, Azra
name: Delgado, Graciela E.
name: Jackson, Anne U.
name: Lorés-Motta, Laura
name: Zhao, Jing-Hua
name: Tsao, Philip S.
name: Oldehinkel, Albertine J.
name: Kentistou, Katherine A.
name: Smyth, Laura J.
name: Linneberg, Allan
name: Homuth, Georg
name: McKnight, Amy Jayne
name: Männikkö, Minna
name: Hakonarson, Hakon
name: Franke, Andre
name: Brown, Michael R.
name: Kovacs, Peter
name: Namjou, Bahram
name: Lee, Jiwon
name: Böger, Carsten A.
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name: Rallidis, Loukianos S.
name: Kumari, Meena
name: Sever, Peter
name: Lo, Ken Sin
name: Mercader, Josep M.
name: Boehnke, Michael
name: Rasheed, Humaira
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name: Ingelsson, Erik
name: den Hollander, Anneke I.
name: Snieder, Harold
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name: Tönjes, Anke
name: Hishigaki, Haretsugu
name: Marouli, Eirini
name: Forer, Lukas
name: Mangino, Massimo
name: Zeggini, Eleftheria
name: Niinikoski, Harri
name: Chen, Yii-Der Ida
name: Marques-Vidal, Pedro
name: Deloukas, Panos
name: Zilhao, Nuno R.
name: Raitakari, Olli T.
name: Lynch, Julie A.
name: Mitchell, Ruth E.
name: Hottenga, Jouke Jan
name: Lingren, Todd
name: Abbas, Shahid
name: Redline, Susan
name: Wang, Ya Xing
name: Jöckel, Karl-Heinz
name: Cucca, Francesco
name: Schmidt, Börge
name: Ritchie, Marylyn D.
name: Weir, David R.
name: Ekoru, Kenneth
name: Yu, Ketian
name: Ridker, Paul M.
name: Tabara, Yasuharu
name: Ramsay, Michèle
name: Loukola, Anu
name: Kawaguchi, Takahisa
name: Hansen, Torben
name: Munz, Matthias
name: Wielscher, Matthias
name: Zhou, Wei
name: Concas, Maria Pina
name: North, Kari E.
name: Miller, Jason E.
name: Gieger, Christian
name: Goel, Anuj
name: Wild, Sarah H.
name: Beulens, Joline W. J.
name: Tardif, Jean-Claude
name: van Duijn, Cornelia M.
name: Thiery, Joachim
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name: Hildalgo, Bertha
name: van der Laan, Sander W.
name: Hewitt, Alex W.
name: Pedersen, Oluf
name: Biino, Ginevra
name: Tusié-Luna, Teresa
name: Kivimaki, Mika
name: Xue, Chao
name: Bharadwaj, Dwaipayan
name: Nethander, Maria
name: Cruz, Miguel
name: Wang, Carol A.
name: Hunt, Karen A.
name: Irvin, Marguerite R.
name: Hayward, Caroline
name: Christofidou, Paraskevi
name: Kuusisto, Johanna
name: Pajukanta, Päivi
name: Saleheen, Danish
name: Arnett, Donna K.
name: Nabika, Toru
name: Schmidt, Helena
name: Pacheco, Jennifer Allen
name: Nelson, Amanda E.
name: Rader, Daniel J.
name: Li, Xiaohui
name: Mook-Kanamori, Dennis O.
name: Wei, Wen B.
name: Arbeeva, Liubov
name: Bielak, Lawrence F.
name: Schmidt, Ellen M.
name: Jousilahti, Pekka
name: De Jager, Philip L.
name: Clarke, Shoa L.
name: Hunt, Steven C.
name: Zajac, Greg J. M.
name: Wareham, Nicholas J.
name: Daviglus, Martha
name: Trembath, Richard C.
name: Yang, Jian
name: Wang, Jun-Sing
name: Zeng, Lingyao
name: Golightly, Yvonne M.
name: Munroe, Patricia B.
name: Campbell, Archie
name: Cupples, L. Adrienne
name: Gudbjartsson, Daniel F.
name: Fernandez-Lopez, Juan Carlos
name: Lettre, Guillaume
name: Sabater-Lleal, Maria
name: Wilson, James G.
name: Lu, Fan
name: van Heel, David A.
name: Wilson, James F.
name: Rotimi, Charles N.
name: Matsuda, Fumihiko
name: Zhu, Xiang
name: Salomaa, Veikko
name: Kato, Norihiro
name: Lee, Jong Young
name: Gorski, Mathias
name: Li, Xiaoyin
name: Bentley, Amy R.
name: Sabanayagam, Charumathi
name: Preuss, Michael
name: Karpe, Fredrik
name: Yokota, Mitsuhiro
name: Highland, Heather M.
name: Chen, Shufeng
name: Huang, Hongyan
name: Obura, Morgan O.
name: Holmes, Michael V.
name: Schulze, Matthias B.
name: Couture, Christian
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name: Erdmann, Jeanette
name: Thorleifsson, Gudmar
name: van Meurs, Joyce B. J.
name: Abecasis, Goncalo
Publisher: name: Springer Nature
Year: 2021

description: <p>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&ndash;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&thinsp;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&thinsp;295,000 individuals from 7&thinsp;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.</p>