The power of genetic diversity in genome-wide association studies of lipids
Sarah E Graham 1, Shoa L Clarke # 2 3, Kuan-Han H Wu # 4, Stavroula Kanoni # 5, Greg J M Zajac # 6, Shweta Ramdas # 7, Ida Surakka 1, Ioanna Ntalla 8, Sailaja Vedantam 9 10, Thomas W Winkler 11, Adam E Locke 12, Eirini Marouli 5, Mi Yeong Hwang 13, Sohee Han 13, Akira Narita 14, Ananyo Choudhury 15, Amy R Bentley 16, Kenneth Ekoru 16, Anurag Verma 7, Bhavi Trivedi 17, Hilary C Martin 18, Karen A Hunt 17, Qin Hui 19 20, Derek Klarin 21 22 23, Xiang Zhu 2 24 25 26, Gudmar Thorleifsson 27, Anna Helgadottir 27, Daniel F Gudbjartsson 27 28, Hilma Holm 27, Isleifur Olafsson 29, Masato Akiyama 30 31, Saori Sakaue 30 32 33, Chikashi Terao 34, Masahiro Kanai 23 30 35, Wei Zhou 4 36 37, Ben M Brumpton 38 39 40, Humaira Rasheed 38 39, Sanni E Ruotsalainen 41, Aki S Havulinna 41 42, Yogasudha Veturi 43, QiPing Feng 44, Elisabeth A Rosenthal 45, Todd Lingren 46, Jennifer Allen Pacheco 47, Sarah A Pendergrass 48, Jeffrey Haessler 49, Franco Giulianini 50, Yuki Bradford 43, Jason E Miller 43, Archie Campbell 51 52, Kuang Lin 53, Iona Y Millwood 53 54, George Hindy 55, Asif Rasheed 56, Jessica D Faul 57, Wei Zhao 58, David R Weir 57, Constance Turman 59, Hongyan Huang 59, Mariaelisa Graff 60, Anubha Mahajan 61, Michael R Brown 62, Weihua Zhang 63 64 65, Ketian Yu 66, Ellen M Schmidt 66, Anita Pandit 66, Stefan Gustafsson 67, Xianyong Yin 66, Jian'an Luan 68, Jing-Hua Zhao 69, Fumihiko Matsuda 70, Hye-Mi Jang 13, Kyungheon Yoon 13, Carolina Medina-Gomez 71 72, Achilleas Pitsillides 73, Jouke Jan Hottenga 74 75, Gonneke Willemsen 74 76, Andrew R Wood 77, Yingji Ji 77, Zishan Gao 78 79 80, Simon Haworth 81 82, Ruth E Mitchell 81 83, Jin Fang Chai 84, Mette Aadahl 85, Jie Yao 86, Ani Manichaikul 87, Helen R Warren 88 89, Julia Ramirez 88, Jette Bork-Jensen 90, Line L Kårhus 85, Anuj Goel 61 91, Maria Sabater-Lleal 92 93, Raymond Noordam 94, Carlo Sidore 95, Edoardo Fiorillo 96, Aaron F McDaid 97 98, Pedro Marques-Vidal 99, Matthias Wielscher 100, Stella Trompet 101 102, Naveed Sattar 103, Line T Møllehave 85, Betina H Thuesen 85, Matthias Munz 104 105 106, Lingyao Zeng 107 108, Jianfeng Huang 109, Bin Yang 109, Alaitz Poveda 110, Azra Kurbasic 110, Claudia Lamina 111 112, Lukas Forer 111 112, Markus Scholz 113 114, Tessel E Galesloot 115, Jonathan P Bradfield 116, E Warwick Daw 117, Joseph M Zmuda 118, Jonathan S Mitchell 119, Christian Fuchsberger 119, Henry Christensen 120, Jennifer A Brody 121, Mary F Feitosa 117, Mary K Wojczynski 117, Michael Preuss 122, Massimo Mangino 123 124, Paraskevi Christofidou 123, Niek Verweij 125, Jan W Benjamins 125, Jorgen Engmann 126 127, Rachel L Kember 128, Roderick C Slieker 129 130, Ken Sin Lo 131, Nuno R Zilhao 132, Phuong Le 133, Marcus E Kleber 134 135, Graciela E Delgado 134, Shaofeng Huo 136, Daisuke D Ikeda 137, Hiroyuki Iha 137, Jian Yang 138 139, Jun Liu 140, Hampton L Leonard 141 142, Jonathan Marten 143, Börge Schmidt 144, Marina Arendt 144 145, Laura J Smyth 146, Marisa Cañadas-Garre 146, Chaolong Wang 147 148, Masahiro Nakatochi 149, Andrew Wong 150, Nina Hutri-Kähönen 151 152, Xueling Sim 84, Rui Xia 153, Alicia Huerta-Chagoya 154, Juan Carlos Fernandez-Lopez 155, Valeriya Lyssenko 156 157, Meraj Ahmed 158, Anne U Jackson 6, Marguerite R Irvin 159, Christopher Oldmeadow 160, Han-Na Kim 161 162, Seungho Ryu 163 164, Paul R H J Timmers 143 165, Liubov Arbeeva 166, Rajkumar Dorajoo 148, Leslie A Lange 167, Xiaoran Chai 168 169, Gauri Prasad 170 171, Laura Lorés-Motta 172, Marc Pauper 172, Jirong Long 173, Xiaohui Li 86, Elizabeth Theusch 174, Fumihiko Takeuchi 175, Cassandra N Spracklen 176 177, Anu Loukola 41, Sailalitha Bollepalli 41, Sophie C Warner 178 179, Ya Xing Wang 180 181, Wen B Wei 181, Teresa Nutile 182, Daniela Ruggiero 182 183, Yun Ju Sung 184, Yi-Jen Hung 185, Shufeng Chen 109, Fangchao Liu 109, Jingyun Yang 186 187, Katherine A Kentistou 165, Mathias Gorski 11 188, Marco Brumat 189, Karina Meidtner 190 191, Lawrence F Bielak 58, Jennifer A Smith 57 58, Prashantha Hebbar 192, Aliki-Eleni Farmaki 193 194, Edith Hofer 195 196, Maoxuan Lin 197, Chao Xue 1, Jifeng Zhang 1, Maria Pina Concas 198, Simona Vaccargiu 199, Peter J van der Most 200, Niina Pitkänen 201 202, Brian E Cade 203 204, Jiwon Lee 203, Sander W van der Laan 205, Kumaraswamy Naidu Chitrala 206, Stefan Weiss 207, Martina E Zimmermann 11, Jong Young Lee 208, Hyeok Sun Choi 209, Maria Nethander 210 211, Sandra Freitag-Wolf 212, Lorraine Southam 213 214, Nigel W Rayner 18 61 213 215, Carol A Wang 216, Shih-Yi Lin 217 218 219, Jun-Sing Wang 220 221, Christian Couture 222, Leo-Pekka Lyytikäinen 223 224, Kjell Nikus 225 226, Gabriel Cuellar-Partida 227, Henrik Vestergaard 90 228, Bertha Hildalgo 229, Olga Giannakopoulou 5, Qiuyin Cai 173, Morgan O Obura 129, Jessica van Setten 230, Xiaoyin Li 231, Karen Schwander 117, Natalie Terzikhan 72, Jae Hun Shin 209, Rebecca D Jackson 232, Alexander P Reiner 233, Lisa Warsinger Martin 234, Zhengming Chen 53 54, Liming Li 235, Heather M Highland 60, Kristin L Young 60, Takahisa Kawaguchi 70, Joachim Thiery 114 236, Joshua C Bis 121, Girish N Nadkarni 122, Lenore J Launer 237, Huaixing Li 136, Mike A Nalls 141 142, Olli T Raitakari 201 202 238, Sahoko Ichihara 239, Sarah H Wild 240, Christopher P Nelson 178 179, Harry Campbell 165, Susanne Jäger 190 191, Toru Nabika 241, Fahd Al-Mulla 192, Harri Niinikoski 242 243, Peter S Braund 178 179, Ivana Kolcic 244, Peter Kovacs 245, Tota Giardoglou 246, Tomohiro Katsuya 247 248, Konain Fatima Bhatti 5, Dominique de Kleijn 249, Gert J de Borst 249, Eung Kweon Kim 250, Hieab H H Adams 72 251, M Arfan Ikram 72, Xiaofeng Zhu 231, Folkert W Asselbergs 230, Adriaan O Kraaijeveld 230, Joline W J Beulens 129 252, Xiao-Ou Shu 173, Loukianos S Rallidis 253, Oluf Pedersen 90, Torben Hansen 90, Paul Mitchell 254, Alex W Hewitt 255 256, Mika Kähönen 257 258, Louis Pérusse 222 259, Claude Bouchard 260, Anke Tönjes 245, Yii-Der Ida Chen 86, Craig E Pennell 216, Trevor A Mori 261, Wolfgang Lieb 262, Andre Franke 263, Claes Ohlsson 210 264, Dan Mellström 210 265, Yoon Shin Cho 209, Hyejin Lee 266, Jian-Min Yuan 267 268, Woon-Puay Koh 269 270, Sang Youl Rhee 271, Jeong-Taek Woo 271, Iris M Heid 11, Klaus J Stark 11, Henry Völzke 272, Georg Homuth 207, Michele K Evans 273, Alan B Zonderman 273, Ozren Polasek 244, Gerard Pasterkamp 205, Imo E Hoefer 205, Susan Redline 203 204, Katja Pahkala 201 202 274, Albertine J Oldehinkel 275, Harold Snieder 200, Ginevra Biino 276, Reinhold Schmidt 195, Helena Schmidt 277, Y Eugene Chen 1, Stefania Bandinelli 278, George Dedoussis 193, Thangavel Alphonse Thanaraj 192, Sharon L R Kardia 58, Norihiro Kato 175, Matthias B Schulze 190 191 279, Giorgia Girotto 189 280, Bettina Jung 188, Carsten A Böger 188 281 282, Peter K Joshi 165, David A Bennett 186 187, Philip L De Jager 283 284, Xiangfeng Lu 109, Vasiliki Mamakou 285 286, Morris Brown 89 287, Mark J Caulfield 88 89, Patricia B Munroe 88 89, Xiuqing Guo 86, Marina Ciullo 182 183, Jost B Jonas 288 289 290, Nilesh J Samani 178 179, Jaakko Kaprio 41, Päivi Pajukanta 291, Linda S Adair 292 293, Sonny Augustin Bechayda 294 295, H Janaka de Silva 296, Ananda R Wickremasinghe 297, Ronald M Krauss 298, Jer-Yuarn Wu 299, Wei Zheng 173, Anneke I den Hollander 172, Dwaipayan Bharadwaj 171 300, Adolfo Correa 301, James G Wilson 302, Lars Lind 303, Chew-Kiat Heng 304 305, Amanda E Nelson 166 306, Yvonne M Golightly 166 307 308 309, James F Wilson 143 165, Brenda Penninx 310 76, Hyung-Lae Kim 311, John Attia 160 312, Rodney J Scott 160 312, D C Rao 313, Donna K Arnett 314, Mark Walker 315, Heikki A Koistinen 316 317 318, Giriraj R Chandak 158 319, Chittaranjan S Yajnik 320, Josep M Mercader 321 322 323, Teresa Tusié-Luna 324 325 326, Carlos A Aguilar-Salinas 327 328, Clicerio Gonzalez Villalpando 329, Lorena Orozco 330, Myriam Fornage 153 331, E Shyong Tai 84 332, Rob M van Dam 84 332, Terho Lehtimäki 223 224, Nish Chaturvedi 150, Mitsuhiro Yokota 333, Jianjun Liu 148, Dermot F Reilly 334, Amy Jayne McKnight 146, Frank Kee 146, Karl-Heinz Jöckel 144, Mark I McCarthy 48 61 335, Colin N A Palmer 336, Veronique Vitart 143, Caroline Hayward 143, Eleanor Simonsick 337, Cornelia M van Duijn 140, Fan Lu 338, Jia Qu 338, Haretsugu Hishigaki 137, Xu Lin 136, Winfried März 134 339 340, Esteban J Parra 133, Miguel Cruz 341, Vilmundur Gudnason 132 342, Jean-Claude Tardif 131 343, Guillaume Lettre 131 344, Leen M 't Hart 129 130 345, Petra J M Elders 346, Scott M Damrauer 347 348, Meena Kumari 349, Mika Kivimaki 127, Pim van der Harst 125, Tim D Spector 123, Ruth J F Loos 122 350, Michael A Province 117, Bruce M Psaty 351 352, Ivan Brandslund 120 353, Peter P Pramstaller 119, Kaare Christensen 354, Samuli Ripatti 41 355 356, Elisabeth Widén 41, Hakon Hakonarson 357 358, Struan F A Grant 359 358 360, Lambertus A L M Kiemeney 115, Jacqueline de Graaf 115, Markus Loeffler 113 114, Florian Kronenberg 112 361, Dongfeng Gu 109 362, Jeanette Erdmann 363, Heribert Schunkert 107 364, Paul W Franks 110, Allan Linneberg 85 365, J Wouter Jukema 101 366, Amit V Khera 367 368 369 370, Minna Männikkö 371, Marjo-Riitta Jarvelin 100 372 373, Zoltan Kutalik 98 374, Francesco Cucca 375 376, Dennis O Mook-Kanamori 377 378, Ko Willems van Dijk 379 380 381, Hugh Watkins 61 91, David P Strachan 382, Niels Grarup 90, Peter Sever 383, Neil Poulter 384, Jerome I Rotter 86, Thomas M Dantoft 85, Fredrik Karpe 385 386, Matt J Neville 385 386, Nicholas J Timpson 81 83, Ching-Yu Cheng 168 387, Tien-Yin Wong 168 387, Chiea Chuen Khor 148, Charumathi Sabanayagam 168 387, Annette Peters 80 191 388, Christian Gieger 79 80 191, Andrew T Hattersley 389, Nancy L Pedersen 390, Patrik K E Magnusson 390, Dorret I Boomsma 74 75 391, Eco J C de Geus 74 76, L Adrienne Cupples 73 392, Joyce B J van Meurs 71 72, Mohsen Ghanbari 72 393, Penny Gordon-Larsen 292 293, Wei Huang 394, Young Jin Kim 13, Yasuharu Tabara 70, Nicholas J Wareham 68, Claudia Langenberg 68, Eleftheria Zeggini 213 214 395, Johanna Kuusisto 396, Markku Laakso 396, Erik Ingelsson 3 67 397 398, Goncalo Abecasis 66 399, John C Chambers 63 64 400 401, Jaspal S Kooner 64 65 402 383, Paul S de Vries 62, Alanna C Morrison 62, Kari E North 60, Martha Daviglus 403, Peter Kraft 59 404, Nicholas G Martin 405, John B Whitfield 405, Shahid Abbas 56 406, Danish Saleheen 56 407 408, Robin G Walters 53 54 409, Michael V Holmes 53 54 410, Corri Black 411, Blair H Smith 412, Anne E Justice 413, Aris Baras 399, Julie E Buring 50 321, Paul M Ridker 50 321, Daniel I Chasman 50 321, Charles Kooperberg 49, Wei-Qi Wei 414, Gail P Jarvik 415, Bahram Namjou 416, M Geoffrey Hayes 417 418 419, Marylyn D Ritchie 43, Pekka Jousilahti 42, Veikko Salomaa 42, Kristian Hveem 38 420 421, Bjørn Olav Åsvold 38 420 422, Michiaki Kubo 423, Yoichiro Kamatani 30 424, Yukinori Okada 30 32 425 426, Yoshinori Murakami 427, Unnur Thorsteinsdottir 27 342, Kari Stefansson 27 342, Yuk-Lam Ho 428, Julie A Lynch 429 430, Daniel J Rader 359 431, Philip S Tsao 2 3 432, Kyong-Mi Chang 431 433, Kelly Cho 428 434, Christopher J O'Donnell 428 434, John M Gaziano 428 434, Peter Wilson 435 436, Charles N Rotimi 16, Scott Hazelhurst 15 437, Michèle Ramsay 15 438, Richard C Trembath 439, David A van Heel 17, Gen Tamiya 14, Masayuki Yamamoto 14, Bong-Jo Kim 13, Karen L Mohlke 176, Timothy M Frayling 77, Joel N Hirschhorn 9 10 440, Sekar Kathiresan 368 370 441; VA Million Veteran Program; Global Lipids Genetics Consortium*; Michael Boehnke 6, Pradeep Natarajan 37 442 443 444, Gina M Peloso 73, Christopher D Brown 7, Andrew P Morris 445, Themistocles L Assimes 446 447 448, Panos Deloukas 5 89 449, Yan V Sun 19 20, Cristen J Willer 450 451 452 453
Affiliations
Affiliations
- Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
- VA Palo Alto Health Care System, Palo Alto, CA, USA.
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
- William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Department of Biostatistics and Center for Statistics Genetics, University of Michigan, Ann Arbor, MI, USA.
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Endocrinology, Boston Children's Hospital, Boston, MA, USA.
- Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
- McDonnell Genome Institute and Department of Medicine, Washington University, St Louis, MO, USA.
- Department of Precision Medicine, Division of Genome Science, National Institute of Health, Cheongju-si, South Korea.
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Wellcome Sanger Institute, Hinxton, UK.
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
- Atlanta VA Health Care System, Decatur, GA, USA.
- Malcolm Randall VA Medical Center, Gainesville, FL, USA.
- Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, USA.
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Department of Statistics, The Pennsylvania State University, University Park, PA, USA.
- Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
- Department of Statistics, Stanford University, Stanford, CA, USA.
- deCODE genetics/Amgen, Reykjavik, Iceland.
- School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
- Department of Clinical Biochemistry, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland.
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
- Department of Thoracic Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
- Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
- Department of Genetics, Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA.
- Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Center for Genetic Medicine, Northwestern University, Evanston, IL, USA.
- Genentech, South San Francisco, CA, USA.
- Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA.
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
- Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
- Usher Institute for Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- Department of Population Medicine, Qatar University College of Medicine, QU Health, Doha, Qatar.
- Center for Non-Communicable Diseases, Karachi, Pakistan.
- Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
- Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
- Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
- Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, Southall, UK.
- Imperial College Healthcare NHS Trust, London, UK.
- Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
- Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge Strangeways Research Laboratory, Cambridge, UK.
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
- Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
- Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
- Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
- Department of Biological Psychology, Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- Amsterdam Public Health, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
- Amsterdam Public Health Research Institute, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
- Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
- Department of Clinical Acupuncture and Moxibustion, Nanjing University of Chinese Medicine, Nanjing, China.
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
- Bristol Dental School, University of Bristol, Bristol, UK.
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovations (Formerly LABioMed) at Harbor-UCLA Medical Center, Torrance, CA, USA.
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Queen Mary University of London, London, UK.
- NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
- Group of Genomics of Complex Diseases, Research Institute of Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), Barcelona, Spain.
- Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
- Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
- Institute for Genetic and Biomedical Research, Italian National Council of Research (IRGB CNR), Cagliari,, Italy.
- Institute for Genetic and Biomedical Research, Italian National Council of Research (IRGB CNR), Lanusei, Italy.
- University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
- Swiss Institute of Bioinformatics, Lausanne, Switzerland.
- Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
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.
References
https://pubmed.ncbi.nlm.nih.gov/