@article{3033399,
    title = "The power of genetic diversity in genome-wide association studies of
lipids",
    author = "Graham, Sarah E. and Clarke, Shoa L. and Wu, Kuan-Han H. and Kanoni, and Stavroula and Zajac, Greg J. M. and Ramdas, Shweta and Surakka, Ida and and Ntalla, Ioanna and Vedantam, Sailaja and Winkler, Thomas W. and Locke, and Adam E. and Marouli, Eirini and Hwang, Mi Yeong and Han, Sohee and and Narita, Akira and Choudhury, Ananyo and Bentley, Amy R. and Ekoru, and Kenneth and Verma, Anurag and Trivedi, Bhavi and Martin, Hilary C. and and Hunt, Karen A. and Hui, Qin and Klarin, Derek and Zhu, Xiang and and Thorleifsson, Gudmar and Helgadottir, Anna and Gudbjartsson, Daniel F. and and Holm, Hilma and Olafsson, Isleifur and Akiyama, Masato and Sakaue, and Saori and Terao, Chikashi and Kanai, Masahiro and Zhou, Wei and and Brumpton, Ben M. and Rasheed, Humaira and Ruotsalainen, Sanni E. and and Havulinna, Aki S. and Veturi, Yogasudha and Feng, QiPing and Rosenthal, and Elisabeth A. and Lingren, Todd and Pacheco, Jennifer Allen and and Pendergrass, Sarah A. and Haessler, Jeffrey and Giulianini, Franco and and Bradford, Yuki and Miller, Jason E. and Campbell, Archie and Lin, Kuang and and Millwood, Iona Y. and Hindy, George and Rasheed, Asif and Faul, and Jessica D. and Zhao, Wei and Weir, David R. and Turman, Constance and and Huang, Hongyan and Graff, Mariaelisa and Mahajan, Anubha and Brown, and Michael R. and Zhang, Weihua and Yu, Ketian and Schmidt, Ellen M. and and Pandit, Anita and Gustafsson, Stefan and Yin, Xianyong and Luan, Jian'an and and Zhao, Jing-Hua and Matsuda, Fumihiko and Jang, Hye-Mi and Yoon, and Kyungheon and Medina-Gomez, Carolina and Pitsillides, Achilleas and and Hottenga, Jouke Jan and Willemsen, Gonneke and Wood, Andrew R. and Ji, and Yingji and Gao, Zishan and Haworth, Simon and Mitchell, Ruth E. and and Chai, Jin Fang and Aadahl, Mette and Yao, Jie and Manichaikul, Ani and and Warren, Helen R. and Ramirez, Julia and Bork-Jensen, Jette and Karhus, and Line L. and Goel, Anuj and Sabater-Lleal, Maria and Noordam, Raymond and and Sidore, Carlo and Fiorillo, Edoardo and McDaid, Aaron F. and and Marques-Vidal, Pedro and Wielscher, Matthias and Trompet, Stella and and Sattar, Naveed and Mollehave, Line T. and Thuesen, Betina H. and Munz, and Matthias and Zeng, Lingyao and Huang, Jianfeng and Yang, Bin and Poveda, and Alaitz and Kurbasic, Azra and Lamina, Claudia and Forer, Lukas and and Scholz, Markus and Galesloot, Tessel E. and Bradfield, Jonathan P. and and Daw, E. Warwick and Zmuda, Joseph M. and Mitchell, Jonathan S. and and Fuchsberger, Christian and Christensen, Henry and Brody, Jennifer A. and and Feitosa, Mary F. and Wojczynski, Mary K. and Preuss, Michael and and Mangino, Massimo and Christofidou, Paraskevi and Verweij, Niek and and Benjamins, Jan W. and Engmann, Jorgen and Kember, Rachel L. and Slieker, and Roderick C. and Lo, Ken Sin and Zilhao, Nuno R. and Phuong Le and and Kleber, Marcus E. and Delgado, Graciela E. and Huo, Shaofeng and Ikeda, and Daisuke D. and Iha, Hiroyuki and Yang, Jian and Liu, Jun and Leonard, and Hampton L. and Marten, Jonathan and Schmidt, Borge and Arendt, Marina and and Smyth, Laura J. and Canadas-Garre, Marisa and Wang, Chaolong and and Nakatochi, Masahiro and Wong, Andrew and Hutri-Kahonen, Nina and Sim, and Xueling and Xia, Rui and Huerta-Chagoya, Alicia and Fernandez-Lopez, and Juan Carlos and Lyssenko, Valeriya and Ahmed, Meraj and Jackson, Anne U. and and Irvin, Marguerite R. and Oldmeadow, Christopher and Kim, Han-Na and and Ryu, Seungho and Timmers, Paul R. H. J. and Arbeeva, Liubov and Dorajoo, and Rajkumar and Lange, Leslie A. and Chai, Xiaoran and Prasad, Gauri and and Lores-Motta, Laura and Pauper, Marc and Long, Jirong and Li, Xiaohui and and Theusch, Elizabeth and Takeuchi, Fumihiko and Spracklen, Cassandra N. and and Loukola, Anu and Bollepalli, Sailalitha and Warner, Sophie C. and and Wang, Ya Xing and Wei, Wen B. and Nutile, Teresa and Ruggiero, Daniela and and Sung, Yun Ju and Hung, Yi-Jen and Chen, Shufeng and Liu, Fangchao and and Yang, Jingyun and Kentistou, Katherine A. and Gorski, Mathias and and Brumat, Marco and Meidtner, Karina and Bielak, Lawrence F. and Smith, and Jennifer A. and Hebbar, Prashantha and Farmaki, Aliki-Eleni and Hofer, and Edith and Lin, Maoxuan and Xue, Chao and Zhang, Jifeng and Concas, Maria and Pina and Vaccargiu, Simona and van der Most, Peter J. and Pitkanen, and Niina and Cade, Brian E. and Lee, Jiwon and van Der Laan, Sander W. and and Chitrala, Kumaraswamy Naidu and Weiss, Stefan and Zimmermann, Martina E. and and Lee, Jong Young and Choi, Hyeok Sun and Nethander, Maria and and Freitag-Wolf, Sandra and Southam, Lorraine and Rayner, Nigel W. and and Wang, Carol A. and Lin, Shih-Yi and Wang, Jun-Sing and Couture, and Christian and Lyytikainen, Leo-Pekka and Nikus, Kjell and and Cuellar-Partida, Gabriel and Vestergaard, Henrik and Hildalgo, Bertha and and Giannakopoulou, Olga and Cai, Qiuyin and Obura, Morgan O. and van and Setten, Jessica and Li, Xiaoyin and Schwander, Karen and Terzikhan, and Natalie and Shin, Jae Hun and Jackson, Rebecca D. and Reiner, Alexander and P. and Martin, Lisa Warsinger and Chen, Zhengming and Li, Liming and and Highland, Heather M. and Young, Kristin L. and Kawaguchi, Takahisa and and Thiery, Joachim and Bis, Joshua C. and Nadkarni, Girish N. and Launer, and Lenore J. and Li, Huaixing and Nalls, Mike A. and Raitakari, Olli T. and and Ichihara, Sahoko and Wild, Sarah H. and Nelson, Christopher P. and and Campbell, Harry and Jager, Susanne and Nabika, Toru and Al-Mulla, Fahd and and Niinikoski, Harri and Braund, Peter S. and Kolcic, Ivana and Kovacs, and Peter and Giardoglou, Tota and Katsuya, Tomohiro and Bhatti, Fatima and and de Kleijn, Dominique and de Borst, Gert J. and Kim, Eung Kweon and and Adams, Hieab H. H. and Ikram, M. Arfan and Zhu, Xiaofeng and Asselbergs, and Folkert W. and Kraaijeveld, Adriaan O. and Beulens, Joline W. J. and and Shu, Xiao-Ou and Rallidis, Loukianos S. and Pedersen, Oluf and Hansen, and Torben and Mitchell, Paul and Hewitt, Alex W. and Kahonen, Mika and and Perusse, Louis and Bouchard, Claude and Tonjes, Anke and Chen, Yii-Der and Ida and Pennell, Craig E. and Mori, Trevor A. and Lieb, Wolfgang and and Franke, Andre and Ohlsson, Claes and Mellstrom, Dan and Cho, Yoon Shin and and Lee, Hyejin and Yuan, Jian-Min and Koh, Woon-Puay and Rhee, Sang and Youl and Woo, Jeong-Taek and Heid, Iris M. and Stark, Klaus J. and and Volzke, Henry and Homuth, Georg and Evans, Michele K. and Zonderman, and Alan B. and Polasek, Ozren and Pasterkamp, Gerard and Hoefer, Imo E. and and Redline, Susan and Pahkala, Katja and Oldehinkel, Albertine J. and and Snieder, Harold and Biino, Ginevra and Schmidt, Reinhold and Schmidt, and Helena and Chen, Y. Eugene and Bandinelli, Stefania and Dedoussis, and George and Thanaraj, Thangavel Alphonse and Kardia, Sharon L. R. and and Kato, Norihiro and Schulze, Matthias B. and Girotto, Giorgia and Jung, and Bettina and Boger, Carsten A. and Joshi, Peter K. and Bennett, David A. and and De Jager, Philip L. and Lu, Xiangfeng and Mamakou, Vasiliki and and Brown, Morris and Caulfield, Mark J. and Munroe, Patricia B. and Guo, and Xiuqing and Ciullo, Marina and Jonas, Jost B. and Samani, Nilesh J. and and Kaprio, Jaakko and Pajukanta, Paivi and Adair, Linda S. and Bechayda, and Sonny Augustin and de Silva, H. Janaka and Wickremasinghe, Ananda R. and and Krauss, Ronald M. and Wu, Jer-Yuarn and Zheng, Wei and den Hollander, I, and Anneke and Bharadwaj, Dwaipayan and Correa, Adolfo and Wilson, James G. and and Lind, Lars and Heng, Chew-Kiat and Nelson, Amanda E. and Golightly, and Yvonne M. and Wilson, James F. and Penninx, Brenda and Kim, Hyung-Lae and and Attia, John and Scott, Rodney J. and Rao, D. C. and Arnett, Donna K. and and Walker, Mark and Koistinen, Heikki A. and Chandak, Giriraj R. and and Yajnik, Chittaranjan S. and Mercader, Josep M. and Tusie-Luna, Teresa and and Aguilar-Salinas, Carlos A. and Villalpando, Clicerio Gonzalez and and Orozco, Lorena and Fornage, Myriam and Tai, E. Shyong and van Dam, Rob and M. and Lehtimaki, Terho and Chaturvedi, Nish and Yokota, Mitsuhiro and and Liu, Jianjun and Reilly, Dermot F. and McKnight, Amy Jayne and Kee, and Frank and Jockel, Karl-Heinz and McCarthy, I, Mark and Palmer, Colin N. and A. and Vitart, Veronique and Hayward, Caroline and Simonsick, Eleanor and and van Duijn, Cornelia M. and Lu, Fan and Qu, Jia and Hishigaki, and Haretsugu and Lin, Xu and Marz, Winfried and Parra, Esteban J. and Cruz, and Miguel and Gudnason, Vilmundur and Tardif, Jean-Claude and Lettre, and Guillaume and `t Hart, Leen M. and Elders, Petra J. M. and Damrauer, and Scott M. and Kumari, Meena and Kivimaki, Mika and van der Harst, Pim and and Spector, Tim D. and Loos, Ruth J. F. and Province, Michael A. and Psaty, and Bruce M. and Brandslund, Ivan and Pramstaller, Peter P. and Christensen, and Kaare and Ripatti, Samuli and Widen, Elisabeth and Hakonarson, Hakon and and Grant, Struan F. A. and Kiemeney, Lambertus A. L. M. and de Graaf, and Jacqueline and Loeffler, Markus and Kronenberg, Florian and Gu, Dongfeng and and Erdmann, Jeanette and Schunkert, Heribert and Franks, Paul W. and and Linneberg, Allan and Jukema, J. Wouter and Khera, V, Amit and Mannikko, and Minna and Jarvelin, Marjo-Riitta and Kutalik, Zoltan and Cucca, and Francesco and Mook-Kanamori, Dennis O. and van Dijk, Ko Willems and and Watkins, Hugh and Strachan, David P. and Grarup, Niels and Sever, Peter and and Poulter, Neil and Rotter, I, Jerome and Dantoft, Thomas M. and and Karpe, Fredrik and Neville, Matt J. and Timpson, Nicholas J. and Cheng, and Ching-Yu and Wong, Tien-Yin and Khor, Chiea Chuen and Sabanayagam, and Charumathi and Peters, Annette and Gieger, Christian and Hattersley, and Andrew T. and Pedersen, Nancy L. and Magnusson, Patrik K. E. and and Boomsma, I, Dorret and de Geus, Eco J. C. and Cupples, L. Adrienne and and van Meurs, Joyce B. J. and Ghanbari, Mohsen and Rsen, Penny Gordon-La and and Huang, Wei and Kim, Young Jin and Tabara, Yasuharu and Wareham, and Nicholas J. and Langenberg, Claudia and Zeggini, Eleftheria and and Kuusisto, Johanna and Laakso, Markku and Ingelsson, Erik and Abecasis, and Goncalo and Chambers, John C. and Kooner, Jaspal S. and de Vries, Paul and S. and Morrison, Alanna C. and North, Kari E. and Daviglus, Martha and and Kraft, Peter and Martin, Nicholas G. and Whitfield, John B. and Abbas, and Shahid and Saleheen, Danish and Walters, Robin G. and Holmes, V, Michael and and Black, Corri and Smith, Blair H. and Justice, Anne E. and Baras, and Aris and Buring, Julie E. and Ridker, Paul M. and Chasman, I, Daniel and and Kooperberg, Charles and Wei, Wei-Qi and Jarvik, Gail P. and Namjou, and Bahram and Hayes, M. Geoffrey and Ritchie, Marylyn D. and Jousilahti, and Pekka and Salomaa, Veikko and Hveem, Kristian and Asvold, Bjorn Olav and and Kubo, Michiaki and Kamatani, Yoichiro and Okada, Yukinori and Murakami, and Yoshinori and Thorsteinsdottir, Unnur and Stefansson, Kari and Ho, and Yuk-Lam and Lynch, Julie A. and Rader, Daniel J. and Tsao, Philip S. and and Chang, Kyong-Mi and Cho, Kelly and O'Donnell, Christopher J. and and Gaziano, John M. and Wilson, Peter and Rotimi, Charles N. and and Hazelhurst, Scott and Ramsay, Michele and Trembath, Richard C. and van and Heel, David A. and Tamiya, Gen and Yamamoto, Masayuki and Kim, Bong-Jo and and Mohlke, Karen L. and Frayling, Timothy M. and Hirschhorn, Joel N. and and Kathiresan, Sekar and Boehnke, Michael and Natarajan, Pradeep and and Peloso, Gina M. and Brown, Christopher D. and Morris, Andrew P. and and Assimes, Themistocles L. and Deloukas, Panos and Sun, V, Yan and Willer, and Cristen J.",
    journal = "Nature",
    year = "2021",
    volume = "600",
    number = "7890",
    pages = "675+",
    publisher = "NATURE PORTFOLIO",
    issn = "0028-0836",
    doi = "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 use(1). Despite advances in
prevention and treatment, in particular through reducing low-density
lipoprotein cholesterol levels(2), heart disease remains the leading
cause of death worldwide(3). 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(4-23) 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 patterns(24). 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(25), we
anticipate that increased diversity of participants will lead to more
accurate and equitable(26) application of polygenic scores in clinical
practice."
}