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Warwick and Zmuda, Joseph M. and Mitchell, Jonathan S. and Fuchsberger, Christian and Christensen, Henry and Brody, Jennifer A. and Feitosa, Mary F. and Wojczynski, Mary K. and Preuss, Michael and Mangino, Massimo and Christofidou, Paraskevi and Verweij, Niek and Benjamins, Jan W. and Engmann, Jorgen and Kember, Rachel L. and Slieker, Roderick C. and Lo, Ken Sin and Zilhao, Nuno R. and Phuong Le, and Kleber, Marcus E. and Delgado, Graciela E. and Huo, Shaofeng and Ikeda, Daisuke D. and Iha, Hiroyuki and Yang, Jian and Liu, Jun and Leonard, Hampton L. and Marten, Jonathan and Schmidt, Borge and Arendt, Marina and Smyth, Laura J. and Canadas-Garre, Marisa and Wang, Chaolong and Nakatochi, Masahiro and Wong, Andrew and Hutri-Kahonen, Nina and Sim, Xueling and Xia, Rui and Huerta-Chagoya, Alicia and Fernandez-Lopez, Juan Carlos and Lyssenko, Valeriya and Ahmed, Meraj and Jackson, Anne U. and Irvin, Marguerite R. and Oldmeadow, Christopher and Kim, Han-Na and Ryu, Seungho and Timmers, Paul R. 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H. and Ikram, M. Arfan and Zhu, Xiaofeng and Asselbergs, Folkert W. and Kraaijeveld, Adriaan O. and Beulens, Joline W. J. and Shu, Xiao-Ou and Rallidis, Loukianos S. and Pedersen, Oluf and Hansen, Torben and Mitchell, Paul and Hewitt, Alex W. and Kahonen, Mika and Perusse, Louis and Bouchard, Claude and Tonjes, Anke and Chen, Yii-Der Ida and Pennell, Craig E. and Mori, Trevor A. and Lieb, Wolfgang and Franke, Andre and Ohlsson, Claes and Mellstrom, Dan and Cho, Yoon Shin and Lee, Hyejin and Yuan, Jian-Min and Koh, Woon-Puay and Rhee, Sang Youl and Woo, Jeong-Taek and Heid, Iris M. and Stark, Klaus J. and Volzke, Henry and Homuth, Georg and Evans, Michele K. and Zonderman, Alan B. and Polasek, Ozren and Pasterkamp, Gerard and Hoefer, Imo E. and Redline, Susan and Pahkala, Katja and Oldehinkel, Albertine J. and Snieder, Harold and Biino, Ginevra and Schmidt, Reinhold and Schmidt, Helena and Chen, Y. Eugene and Bandinelli, Stefania and Dedoussis, George and Thanaraj, Thangavel Alphonse and Kardia, Sharon L. R. and Kato, Norihiro and Schulze, Matthias B. and Girotto, Giorgia and Jung, Bettina and Boger, Carsten A. and Joshi, Peter K. and Bennett, David A. and De Jager, Philip L. and Lu, Xiangfeng and Mamakou, Vasiliki and Brown, Morris and Caulfield, Mark J. and Munroe, Patricia B. and Guo, Xiuqing and Ciullo, Marina and Jonas, Jost B. and Samani, Nilesh J. and Kaprio, Jaakko and Pajukanta, Paivi and Adair, Linda S. and Bechayda, Sonny Augustin and de Silva, H. Janaka and Wickremasinghe, Ananda R. and Krauss, Ronald M. and Wu, Jer-Yuarn and Zheng, Wei and den Hollander, Anneke and Bharadwaj, Dwaipayan and Correa, Adolfo and Wilson, James G. and Lind, Lars and Heng, Chew-Kiat and Nelson, Amanda E. and Golightly, Yvonne M. and Wilson, James F. and Penninx, Brenda and Kim, Hyung-Lae and Attia, John and Scott, Rodney J. and Rao, D. 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Geoffrey and Ritchie, Marylyn D. and Jousilahti, Pekka and Salomaa, Veikko and Hveem, Kristian and Asvold, Bjorn Olav and Kubo, Michiaki and Kamatani, Yoichiro and Okada, Yukinori and Murakami, Yoshinori and Thorsteinsdottir, Unnur and Stefansson, Kari and Ho, Yuk-Lam and Lynch, Julie A. and Rader, Daniel J. and Tsao, Philip S. and Chang, Kyong-Mi and Cho, Kelly and O'Donnell, Christopher J. and Gaziano, John M. and Wilson, Peter and Rotimi, Charles N. and Hazelhurst, Scott and Ramsay, Michele and Trembath, Richard C. and van Heel, David A. and Tamiya, Gen and Yamamoto, Masayuki and Kim, Bong-Jo and Mohlke, Karen L. and Frayling, Timothy M. and Hirschhorn, Joel N. and Kathiresan, Sekar and Boehnke, Michael and Natarajan, Pradeep and Peloso, Gina M. and Brown, Christopher D. and Morris, Andrew P. and Assimes, Themistocles L. and Deloukas, Panos and Sun, Yan and Willer, Cristen J. (2021) The power of genetic diversity in genome-wide association studies of lipids. NATURE, 600 (7890). pp. 675-679. ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOW-FREQUENCY; LOCI; METAANALYSIS; CHOLESTEROL; ANCESTRY; POLYMORPHISMS; DISCOVERY; VARIANTS; RISK; INDIVIDUALS |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2022 05:19 |
| Last Modified: | 05 Jul 2022 05:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48245 |
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