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

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dc.contributor.author Graham, S.E.
dc.contributor.author Clarke, S.L.
dc.contributor.author Wu, K.H.
dc.contributor.author Kanoni, S.
dc.contributor.author Zajac, G.J.M.
dc.contributor.author Ramdas, S.
dc.contributor.author Surakka, I.
dc.contributor.author Ntalla, I.
dc.contributor.author Vedantam, S.
dc.contributor.author Winkler, T.W.
dc.contributor.author Locke, A.E.
dc.contributor.author Marouli, E.
dc.contributor.author Hwang, M.Y.
dc.contributor.author Han, S.
dc.contributor.author Narita, A.
dc.contributor.author Choudhury, A.
dc.contributor.author Bentley, A.R.
dc.contributor.author Ekoru, K.
dc.contributor.author Verma, A.
dc.contributor.author Trivedi, B.
dc.contributor.author Martin, H.C.
dc.contributor.author Hunt, K.A.
dc.contributor.author Hui, Q.
dc.contributor.author Klarin, D.
dc.contributor.author Zhu, X.
dc.contributor.author Thorleifsson, G.
dc.contributor.author Helgadottir, A.
dc.contributor.author Gudbjartsson, D.F.
dc.contributor.author Holm, H.
dc.contributor.author Olafsson, I.
dc.contributor.author Akiyama, M.
dc.contributor.author Sakaue, S.
dc.contributor.author Terao, C.
dc.contributor.author Kanai, M.
dc.contributor.author Zhou, W.
dc.contributor.author Brumpton, B.M.
dc.contributor.author Rasheed, H.
dc.contributor.author Ruotsalainen, S.E.
dc.contributor.author Havulinna, A.S.
dc.contributor.author Veturi, Y.
dc.contributor.author Feng, Q.
dc.contributor.author Rosenthal, E.A.
dc.contributor.author Lingren, T.
dc.contributor.author Pacheco, J.A.
dc.contributor.author Pendergrass, S.A.
dc.contributor.author Haessler, J.
dc.contributor.author Giulianini, F.
dc.contributor.author Bradford, Y.
dc.contributor.author Miller, J.E.
dc.contributor.author Campbell, A.
dc.contributor.author Lin, K.
dc.contributor.author Millwood, I.Y.
dc.contributor.author Hindy, G.
dc.contributor.author Rasheed, A.
dc.contributor.author Faul, J.D.
dc.contributor.author Zhao, W.
dc.contributor.author Weir, D.R.
dc.contributor.author Turman, C.
dc.contributor.author Huang, H.
dc.contributor.author Graff, M.
dc.contributor.author Mahajan, A.
dc.contributor.author Brown, M.R.
dc.contributor.author Zhang, W.
dc.contributor.author Yu, K.
dc.contributor.author Schmidt, E.M.
dc.contributor.author Pandit, A.
dc.contributor.author Gustafsson, S.
dc.contributor.author Yin, X.
dc.contributor.author Luan, J.
dc.contributor.author Zhao, J.H.
dc.contributor.author Matsuda, F.
dc.contributor.author Jang, H.M.
dc.contributor.author Yoon, K.
dc.contributor.author Medina-Gomez, C.
dc.contributor.author Pitsillides, A.
dc.contributor.author Hottenga, J.J.
dc.contributor.author Willemsen, G.
dc.contributor.author Wood, A.R.
dc.contributor.author Ji, Y.
dc.contributor.author Gao, Z.
dc.contributor.author Haworth, S.
dc.contributor.author Mitchell, R.E.
dc.contributor.author Chai, J.F.
dc.contributor.author Aadahl, M.
dc.contributor.author Yao, J.
dc.contributor.author Manichaikul, A.
dc.contributor.author Warren, H.R.
dc.contributor.author Ramirez, J.
dc.contributor.author Bork-Jensen, J.
dc.contributor.author Kårhus, L.L.
dc.contributor.author Goel, A.
dc.contributor.author Sabater-Lleal, M.
dc.contributor.author Noordam, R.
dc.contributor.author Sidore, C.
dc.contributor.author Fiorillo, E.
dc.contributor.author McDaid, A.F.
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dc.contributor.author Sattar, N.
dc.contributor.author Møllehave, L.T.
dc.contributor.author Thuesen, B.H.
dc.contributor.author Munz, M.
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dc.contributor.author Poveda, A.
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dc.contributor.author Delgado, G.E.
dc.contributor.author Huo, S.
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dc.contributor.author Bollepalli, S.
dc.contributor.author Warner, S.C.
dc.contributor.author Wang, Y.X.
dc.contributor.author Wei, W.B.
dc.contributor.author Nutile, T.
dc.contributor.author Ruggiero, D.
dc.contributor.author Sung, Y.J.
dc.contributor.author Hung, Y.J.
dc.contributor.author Chen, S.
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dc.contributor.author Kentistou, K.A.
dc.contributor.author Gorski, M.
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dc.contributor.author Bielak, L.F.
dc.contributor.author Smith, J.A.
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dc.contributor.author Hofer, E.
dc.contributor.author Lin, M.
dc.contributor.author Xue, C.
dc.contributor.author Zhang, J.
dc.contributor.author Concas, M.P.
dc.contributor.author Vaccargiu, S.
dc.contributor.author van der Most, P.J.
dc.contributor.author Pitkänen, N.
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dc.contributor.author van der Laan, S.W.
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dc.contributor.author Freitag-Wolf, S.
dc.contributor.author Southam, L.
dc.contributor.author Rayner, N.W.
dc.contributor.author Wang, C.A.
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dc.contributor.author Wang, J.S.
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dc.contributor.author Niinikoski, H.
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dc.contributor.author Kolcic, I.
dc.contributor.author Kovacs, P.
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dc.contributor.author Bhatti, K.F.
dc.contributor.author de Kleijn, D.
dc.contributor.author de Borst, G.J.
dc.contributor.author Kim, E.K.
dc.contributor.author Adams, H.H.H.
dc.contributor.author Ikram, M.A.
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dc.contributor.author Hansen, T.
dc.contributor.author Mitchell, P.
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dc.contributor.author Pérusse, L.
dc.contributor.author Bouchard, C.
dc.contributor.author Tönjes, A.
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dc.contributor.author Pennell, C.E.
dc.contributor.author Mori, T.A.
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dc.contributor.author Mellström, D.
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dc.contributor.author Homuth, G.
dc.contributor.author Evans, M.K.
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dc.contributor.author Polasek, O.
dc.contributor.author Pasterkamp, G.
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dc.contributor.author Kardia, S.L.R.
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dc.contributor.author Girotto, G.
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dc.contributor.author Kooperberg, C.
dc.contributor.author Wei, W.Q.
dc.contributor.author Jarvik, G.P
dc.contributor.author Namjou, B.
dc.contributor.author Hayes, M.G.
dc.contributor.author Ritchie, M.D.
dc.contributor.author Jousilahti, P.
dc.contributor.author Salomaa, V.
dc.contributor.author Hveem, K.
dc.contributor.author Åsvold, B.O.
dc.contributor.author Kubo, M.
dc.contributor.author Kamatani, Y.
dc.contributor.author Okada, Y.
dc.contributor.author Murakami, Y.
dc.contributor.author Thorsteinsdottir, U.
dc.contributor.author Stefansson, K.
dc.contributor.author Ho, Y.L.
dc.contributor.author Lynch, J.A.
dc.contributor.author Rader, D.J.
dc.contributor.author Tsao, P.S.
dc.contributor.author Chang, K.M.
dc.contributor.author Cho, K.
dc.contributor.author O'Donnell, C.J.
dc.contributor.author Gaziano, J.M.
dc.contributor.author Wilson, P.
dc.contributor.author Rotimi, C.N.
dc.contributor.author Hazelhurst, S.
dc.contributor.author Ramsay, M.
dc.contributor.author Trembath, R.C.
dc.contributor.author van Heel, D.A.
dc.contributor.author Tamiya, G.
dc.contributor.author Yamamoto, M.
dc.contributor.author Kim, B.J.
dc.contributor.author Mohlke, K.L.
dc.contributor.author Frayling, T.M.
dc.contributor.author Hirschhorn, J.N.
dc.contributor.author Kathiresan, S.
dc.contributor.author Boehnke, M.
dc.contributor.author Natarajan, P.
dc.contributor.author Peloso, G.M.
dc.contributor.author Brown, C.D.
dc.contributor.author Morris, A.P.
dc.contributor.author Assimes, T.L.
dc.contributor.author Deloukas, P.
dc.contributor.author Sun, Y.V.
dc.contributor.author Willer, C.J.
dc.contributor.author VA Million Veteran Program
dc.contributor.author Global Lipids Genetics Consortium
dc.date.accessioned 2022-02-18T08:04:35Z
dc.date.available 2022-02-18T08:04:35Z
dc.date.issued 2021
dc.identifier.citation Nature.2021;600(7890):675-679.[[Author Correction: Nature. 2023; 618(7965): E19–E20 ] en_US
dc.identifier.issn 0028-0836
dc.identifier.uri http://repository.kln.ac.lk/handle/123456789/24478
dc.description Indexed in MEDLINE. en_US
dc.description.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. en_US
dc.language.iso en en_US
dc.publisher Macmillan Journals Ltd en_US
dc.subject Risk factors en_US
dc.subject Cardiovascular diseases en_US
dc.title The power of genetic diversity in genome-wide association studies of lipids en_US
dc.type Article en_US


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