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The power of genetic diversity in genome-wide association studies of lipids
Open accessAbstract
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.
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“This result replicated previous studies showing that multi-ancestry PGS demonstrated an improved prediction performance relative to ancestry-matched PGSs41,42.”
From Shared genetic architectures of educational attainment in East Asian and European populations (2024) · cites this paper as [41]
Experimental — accuracy not yet measuredIn the citing paper
“We found genetic variants significantly associated with plasma high-density lipoprotein cholesterol (HDL-c; p < 5.0E-08; Fig. 6a).”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [28]
In the citing paper
“The top-associated single nucleotide polymorphism (SNP), rs10507274, more specifically the “C” allele, found in ~6% of the general population, is significantly associated with increased plasma levels of HDL-c (p = 8.6E-11, Beta = +0.0183 ( ± 2.8E-03); Fig. 6a, b).”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [28]
In the citing paper
“The Global Lipids Genetics Consortium aggregated GWAS results from 1,654,960 individuals from 201 primary studies representing five genetic ancestry groups28.”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [28]
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Metadata
- Authors
- Graham, S. E., Clarke, S. L., Wu, K.-H. H., Kanoni, S., Zajac, G. J. M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T. W., Locke, A. E., Marouli, E., Hwang, M. Y., Han, S., Narita, A., Choudhury, A., Bentley, A. R., Ekoru, K., Verma, A., Trivedi, B., Martin, H. C., Hunt, K. A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D. F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B. M., Rasheed, H., Ruotsalainen, S. E., Havulinna, A. S., Veturi, Y., Feng, Q., Rosenthal, E. A., Lingren, T., Pacheco, J. A., Pendergrass, S. A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J. E., Campbell, A., Lin, K., Millwood, I. Y., Hindy, G., Rasheed, A., Faul, J. D., Zhao, W., Weir, D. R., Turman, C., Huang, H., Graff, M., Mahajan, A., Brown, M. R., Zhang, W., Yu, K., Schmidt, E. M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J.-H., Matsuda, F., Jang, H.-M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J. J., Willemsen, G., Wood, A. R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R. E., Chai, J. F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H. R., Ramirez, J., Bork-Jensen, J., Kårhus, L. L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., McDaid, A. F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Møllehave, L. T., Thuesen, B. H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T. E., Bradfield, J. P., Daw, E. W., Zmuda, J. M., Mitchell, J. S., Fuchsberger, C., Christensen, H., Brody, J. A., Feitosa, M. F., Wojczynski, M. K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J. W., Engmann, J., Kember, R. L., Slieker, R. C., Lo, K. S., Zilhao, N. R., Le, P., Kleber, M. E., Delgado, G. E., Huo, S., Ikeda, D. D., Iha, H., Yang, J., Liu, J., Leonard, H. L., Marten, J., Schmidt, B., Arendt, M., Smyth, L. J., Cañadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kähönen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J. C., Lyssenko, V., Ahmed, M., Jackson, A. U., Yousri, N. A., Irvin, M. R., Oldmeadow, C., Kim, H.-N., Ryu, S., Timmers, P. R. H. J., Arbeeva, L., Dorajoo, R., Lange, L. A., Chai, X., Prasad, G., Lorés-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C. N., Loukola, A., Bollepalli, S., Warner, S. C., Wang, Y. X., Wei, W. B., Nutile, T., Ruggiero, D., Sung, Y. J., Hung, Y.-J., Chen, S., Liu, F., Yang, J., Kentistou, K. A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L. F., Smith, J. A., Hebbar, P., Farmaki, A.-E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M. P., Vaccargiu, S., van der Most, P. J., Pitkänen, N., Cade, B. E., Lee, J., van der Laan, S. W., Chitrala, K. N., Weiss, S., Zimmermann, M. E., Lee, J. Y., Choi, H. S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N. W., Wang, C. A., Lin, S.-Y., Wang, J.-S., Couture, C., Lyytikäinen, L.-P., Nikus, K., Cuellar-Partida, G., Vestergaard, H., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M. O., van Setten, J., Li, X., Schwander, K., Terzikhan, N., Shin, J. H., Jackson, R. D., Reiner, A. P., Martin, L. W., Chen, Z., Li, L., Highland, H. M., Young, K. L., Kawaguchi, T., Thiery, J., Bis, J. C., Nadkarni, G. N., Launer, L. J., Li, H., Nalls, M. A., Raitakari, O. T., Ichihara, S., Wild, S. H., Nelson, C. P., Campbell, H., Jäger, S., Nabika, T., Al-Mulla, F., Niinikoski, H., Braund, P. S., Kolcic, I., Kovacs, P., Giardoglou, T., Katsuya, T., Bhatti, K. F., de Kleijn, D., de Borst, G. J., Kim, E. K., Adams, H. H. H., Ikram, M. A., Zhu, X., Asselbergs, F. W., Kraaijeveld, A. O., Beulens, J. W. J., Shu, X.-O., Rallidis, L. S., Pedersen, O., Hansen, T., Mitchell, P., Hewitt, A. W., Kähönen, M., Pérusse, L., Bouchard, C., Tönjes, A., Chen, Y.-D. I., Pennell, C. E., Mori, T. A., Lieb, W., Franke, A., Ohlsson, C., Mellström, D., Cho, Y. S., Lee, H., Yuan, J.-M., Koh, W.-P., Rhee, S. Y., Woo, J.-T., Heid, I. M., Stark, K. J., Völzke, H., Homuth, G., Evans, M. K., Zonderman, A. B., Polasek, O., Pasterkamp, G., Hoefer, I. E., Redline, S., Pahkala, K., Oldehinkel, A. J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Chen, Y. E., Bandinelli, S., Dedoussis, G., Thanaraj, T. A., Kardia, S. L. R., Kato, N., Schulze, M. B., Girotto, G., Jung, B., Böger, C. A., Joshi, P. K., Bennett, D. A., De Jager, P. L., Lu, X., Mamakou, V., Brown, M., Caulfield, M. J., Munroe, P. B., Guo, X., Ciullo, M., Jonas, J. B., Samani, N. J., Kaprio, J., Pajukanta, P., Adair, L. S., Bechayda, S. A., de Silva, H. J., Wickremasinghe, A. R., Krauss, R. M., Wu, J.-Y., Zheng, W., den Hollander, A. I., Bharadwaj, D., Correa, A., Wilson, J. G., Lind, L., Heng, C.-K., Nelson, A. E., Golightly, Y. M., Wilson, J. F., Penninx, B., Kim, H.-L., Attia, J., Scott, R. J., Rao, D. C., Arnett, D. K., Hunt, S. C., Walker, M., Koistinen, H. A., Chandak, G. R., Yajnik, C. S., Mercader, J. M., Tusié-Luna, T., Aguilar-Salinas, C. A., Villalpando, C. G., Orozco, L., Fornage, M., Tai, E. S., van Dam, R. M., Lehtimäki, T., Chaturvedi, N., Yokota, M., Liu, J., Reilly, D. F., McKnight, A. J., Kee, F., Jöckel, K.-H., McCarthy, M. I., Palmer, C. N. A., Vitart, V., Hayward, C., Simonsick, E., van Duijn, C. M., Lu, F., Qu, J., Hishigaki, H., Lin, X., März, W., Parra, E. J., Cruz, M., Gudnason, V., Tardif, J.-C., Lettre, G., ’t Hart, L. M., Elders, P. J. M., Damrauer, S. M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T. D., Loos, R. J. F., Province, M. A., Psaty, B. M., Brandslund, I., Pramstaller, P. P., Christensen, K., Ripatti, S., Widén, E., Hakonarson, H., Grant, S. F. A., Kiemeney, L. A. L. M., de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P. W., Linneberg, A., Jukema, J. W., Khera, A. V., Männikkö, M., Jarvelin, M.-R., Kutalik, Z., Cucca, F., Mook-Kanamori, D. O., van Dijk, K. W., Watkins, H., Strachan, D. P., Grarup, N., Sever, P., Poulter, N., Rotter, J. I., Dantoft, T. M., Karpe, F., Neville, M. J., Timpson, N. J., Cheng, C.-Y., Wong, T.-Y., Khor, C. C., Sabanayagam, C., Peters, A., Gieger, C., Hattersley, A. T., Pedersen, N. L., Magnusson, P. K. E., Boomsma, D. I., de Geus, E. J. C., Cupples, L. A., van Meurs, J. B. J., Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y. J., Tabara, Y., Wareham, N. J., Langenberg, C., Zeggini, E., Kuusisto, J., Laakso, M., Ingelsson, E., Abecasis, G., Chambers, J. C., Kooner, J. S., de Vries, P. S., Morrison, A. C., North, K. E., Daviglus, M., Kraft, P., Martin, N. G., Whitfield, J. B., Abbas, S., Saleheen, D., Walters, R. G., Holmes, M. V., Black, C., Smith, B. H., Justice, A. E., Baras, A., Buring, J. E., Ridker, P. M., Chasman, D. I., Kooperberg, C., Wei, W.-Q., Jarvik, G. P., Namjou, B., Hayes, M. G., Ritchie, M. D., Jousilahti, P., Salomaa, V., Hveem, K., Åsvold, B. O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Thorsteinsdottir, U., Stefansson, K., Ho, Y.-L., Lynch, J. A., Rader, D. J., Tsao, P. S., Chang, K.-M., Cho, K., O’Donnell, C. J., Gaziano, J. M., Wilson, P., Rotimi, C. N., Hazelhurst, S., Ramsay, M., Trembath, R. C., van Heel, D. A., Tamiya, G., Yamamoto, M., Kim, B.-J., Mohlke, K. L., Frayling, T. M., Hirschhorn, J. N., Kathiresan, S., Program, V. M. V., Global Lipids Genetics Consortium*, Boehnke, M., Natarajan, P., Peloso, G. M., Brown, C. D., Morris, A. P., Assimes, T. L., Deloukas, P., Sun, Y. V., & Willer, C. J.
- Affiliations
- University of Michigan (US)
- VA Palo Alto Health Care System (US)
- Queen Mary University of London (GB)
- University of Pennsylvania (US)
- Broad Institute (US)
- University of Regensburg (DE)
- Washington University in St. Louis (US)
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- Newcastle University (GB)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- National Institute of Genomic Medicine (MX)
- Kurume University (JP)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of Dundee (GB)
- National Institute on Aging (US)
- Wenzhou Medical University (CN)
- Mexican Social Security Institute (MX)
- University of Iceland (IS)
- Philadelphia VA Medical Center (US)
- Kaiser Permanente Washington Health Research Institute (US)
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- Children's Hospital of Philadelphia (US)
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- Imperial College London (GB)
- Churchill Hospital (GB)
- Singapore National Eye Center (SG)
- Helmholtz Munich (DE)
- Karolinska Institutet (SE)
- Mashhad University of Medical Sciences (IR)
- Chinese National Human Genome Center at Shanghai (CN)
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- National Institute for Health and Care Research (GB)
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- Finnish Institute for Health and Welfare (FI)
- Institute of Medical Science, The University of Tokyo (JP)
- VA Boston Healthcare System (US)
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- University of Manchester (GB)
- King Abdulaziz University (SA)
- Corresponding author
- Sun, Yan V.
- ORCID
- Graham, Sarah E.
- Clarke, Shoa L.
- Wu, Kuan-Han H.
- Kanoni, Stavroula
- Zajac, Greg J. M.
- Ramdas, Shweta
- Surakka, Ida
- Vedantam, Sailaja
- Winkler, Thomas W.
- Locke, Adam E.
- Marouli, Eirini
- Hwang, Mi Yeong
- Han, Sohee
- Narita, Akira
- Choudhury, Ananyo
- Bentley, Amy R.
- Ekoru, Kenneth
- Verma, Anurag
- Martin, Hilary C.
- Hunt, Karen A.
- Hui, Qin
- Klarin, Derek
- Zhu, Xiang
- Gudbjartsson, Daniel F.
- Holm, Hilma
- Akiyama, Masato
- Sakaue, Saori
- Terao, Chikashi
- Kanai, Masahiro
- Zhou, Wei
- Brumpton, Ben M.
- Rasheed, Humaira
- Ruotsalainen, Sanni E.
- Havulinna, Aki S.
- Veturi, Yogasudha
- Feng, QiPing
- Rosenthal, Elisabeth A.
- Lingren, Todd
- Pacheco, Jennifer Allen
- Pendergrass, Sarah A.
- Miller, Jason E.
- Campbell, Archie
- Millwood, Iona Y.
- Hindy, George
- Faul, Jessica D.
- Zhao, Wei
- Weir, David R.
- Turman, Constance
- Huang, Hongyan
- Graff, Mariaelisa
- Mahajan, Anubha
- Zhang, Weihua
- Yu, Ketian
- Schmidt, Ellen M.
- Pandit, Anita
- Gustafsson, Stefan
- Yin, Xianyong
- Luan, Jian’an
- Matsuda, Fumihiko
- Jang, Hye-Mi
- Yoon, Kyungheon
- Medina-Gomez, Carolina
- Pitsillides, Achilleas
- Hottenga, Jouke Jan
- Willemsen, Gonneke
- Wood, Andrew R.
- Gao, Zishan
- Haworth, Simon
- Mitchell, Ruth E.
- Chai, Jin Fang
- Aadahl, Mette
- Manichaikul, Ani
- Warren, Helen R.
- Ramirez, Julia
- Kårhus, Line L.
- Goel, Anuj
- Sabater-Lleal, Maria
- Noordam, Raymond
- Sidore, Carlo
- Fiorillo, Edoardo
- McDaid, Aaron F.
- Marques-Vidal, Pedro
- Wielscher, Matthias
- Trompet, Stella
- Sattar, Naveed
- Møllehave, Line T.
- Thuesen, Betina H.
- Munz, Matthias
- Zeng, Lingyao
- Huang, Jianfeng
- Yang, Bin
- Poveda, Alaitz
- Kurbasic, Azra
- Lamina, Claudia
- Forer, Lukas
- Scholz, Markus
- Galesloot, Tessel E.
- Zmuda, Joseph M.
- Fuchsberger, Christian
- Brody, Jennifer A.
- Feitosa, Mary F.
- Wojczynski, Mary K.
- Preuss, Michael
- Mangino, Massimo
- Christofidou, Paraskevi
- Verweij, Niek
- Benjamins, Jan W.
- Engmann, Jorgen
- Kember, Rachel L.
- Slieker, Roderick C.
- Lo, Ken Sin
- Zilhao, Nuno R.
- Le, Phuong
- Kleber, Marcus E.
- Delgado, Graciela E.
- Huo, Shaofeng
- Ikeda, Daisuke D.
- Iha, Hiroyuki
- Yang, Jian
- Liu, Jun
- Leonard, Hampton L.
- Marten, Jonathan
- Schmidt, Börge
- Smyth, Laura J.
- Wang, Chaolong
- Nakatochi, Masahiro
- Wong, Andrew
- Sim, Xueling
- Xia, Rui
- Fernandez-Lopez, Juan Carlos
- Lyssenko, Valeriya
- Jackson, Anne U.
- Yousri, Noha A.
- Irvin, Marguerite R.
- Oldmeadow, Christopher
- Ryu, Seungho
- Timmers, Paul R. H. J.
- Arbeeva, Liubov
- Dorajoo, Rajkumar
- Chai, Xiaoran
- Prasad, Gauri
- Pauper, Marc
- Long, Jirong
- Li, Xiaohui
- Theusch, Elizabeth
- Takeuchi, Fumihiko
- Spracklen, Cassandra N.
- Loukola, Anu
- Bollepalli, Sailalitha
- Warner, Sophie C.
- Wang, Ya Xing
- Wei, Wen B.
- Nutile, Teresa
- Ruggiero, Daniela
- Hung, Yi-Jen
- Chen, Shufeng
- Liu, Fangchao
- Yang, Jingyun
- Kentistou, Katherine A.
- Gorski, Mathias
- Brumat, Marco
- Meidtner, Karina
- Bielak, Lawrence F.
- Smith, Jennifer A.
- Hebbar, Prashantha
- Farmaki, Aliki-Eleni
- Hofer, Edith
- Lin, Maoxuan
- Xue, Chao
- Zhang, Jifeng
- Concas, Maria Pina
- Vaccargiu, Simona
- van der Most, Peter J.
- Pitkänen, Niina
- Cade, Brian E.
- Lee, Jiwon
- van der Laan, Sander W.
- Chitrala, Kumaraswamy Naidu
- Weiss, Stefan
- Zimmermann, Martina E.
- Lee, Jong Young
- Nethander, Maria
- Southam, Lorraine
- Rayner, Nigel W.
- Wang, Carol A.
- Wang, Jun-Sing
- Lyytikäinen, Leo-Pekka
- Nikus, Kjell
- Cuellar-Partida, Gabriel
- Vestergaard, Henrik
- Giannakopoulou, Olga
- Cai, Qiuyin
- van Setten, Jessica
- Schwander, Karen
- Jackson, Rebecca D.
- Reiner, Alexander P.
- Martin, Lisa Warsinger
- Chen, Zhengming
- Li, Liming
- Highland, Heather M.
- Young, Kristin L.
- Kawaguchi, Takahisa
- Thiery, Joachim
- Bis, Joshua C.
- Nadkarni, Girish N.
- Launer, Lenore J.
- Nalls, Mike A.
- Raitakari, Olli T.
- Ichihara, Sahoko
- Wild, Sarah H.
- Nelson, Christopher P.
- Jäger, Susanne
- Nabika, Toru
- Braund, Peter S.
- Kovacs, Peter
- de Kleijn, Dominique
- de Borst, Gert J.
- Kim, Eung Kweon
- Adams, Hieab H. H.
- Ikram, M. Arfan
- Zhu, Xiaofeng
- Asselbergs, Folkert W.
- Kraaijeveld, Adriaan O.
- Beulens, Joline W. J.
- Shu, Xiao-Ou
- Pedersen, Oluf
- Hansen, Torben
- Hewitt, Alex W.
- Kähönen, Mika
- Pérusse, Louis
- Bouchard, Claude
- Tönjes, Anke
- Chen, Yii-Der Ida
- Pennell, Craig E.
- Mori, Trevor A.
- Lieb, Wolfgang
- Ohlsson, Claes
- Mellström, Dan
- Cho, Yoon Shin
- Lee, Hyejin
- Koh, Woon-Puay
- Rhee, Sang Youl
- Woo, Jeong-Taek
- Heid, Iris M.
- Stark, Klaus J.
- Homuth, Georg
- Evans, Michele K.
- Zonderman, Alan B.
- Pasterkamp, Gerard
- Hoefer, Imo E.
- Redline, Susan
- Pahkala, Katja
- Oldehinkel, Albertine J.
- Snieder, Harold
- Biino, Ginevra
- Schmidt, Reinhold
- Schmidt, Helena
- Chen, Y. Eugene
- Bandinelli, Stefania
- Dedoussis, George
- Thanaraj, Thangavel Alphonse
- Kato, Norihiro
- Schulze, Matthias B.
- Girotto, Giorgia
- Joshi, Peter K.
- Bennett, David A.
- De Jager, Philip L.
- Lu, Xiangfeng
- Mamakou, Vasiliki
- Brown, Morris
- Caulfield, Mark J.
- Munroe, Patricia B.
- Guo, Xiuqing
- Ciullo, Marina
- Jonas, Jost B.
- Samani, Nilesh J.
- Kaprio, Jaakko
- Pajukanta, Päivi
- Adair, Linda S.
- de Silva, H. Janaka
- Krauss, Ronald M.
- Zheng, Wei
- den Hollander, Anneke I.
- Bharadwaj, Dwaipayan
- Correa, Adolfo
- Wilson, James G.
- Lind, Lars
- Heng, Chew-Kiat
- Nelson, Amanda E.
- Golightly, Yvonne M.
- Wilson, James F.
- Penninx, Brenda
- Kim, Hyung-Lae
- Attia, John
- Scott, Rodney J.
- Rao, D. C.
- Arnett, Donna K.
- Hunt, Steven C.
- Koistinen, Heikki A.
- Chandak, Giriraj R.
- Yajnik, Chittaranjan S.
- Mercader, Josep M.
- Aguilar-Salinas, Carlos A.
- Orozco, Lorena
- Fornage, Myriam
- Tai, E. Shyong
- van Dam, Rob M.
- Lehtimäki, Terho
- Chaturvedi, Nish
- Liu, Jianjun
- Reilly, Dermot F.
- McKnight, Amy Jayne
- Kee, Frank
- Jöckel, Karl-Heinz
- McCarthy, Mark I.
- Hayward, Caroline
- Simonsick, Eleanor
- van Duijn, Cornelia M.
- Qu, Jia
- März, Winfried
- Parra, Esteban J.
- Cruz, Miguel
- Gudnason, Vilmundur
- Tardif, Jean-Claude
- Lettre, Guillaume
- Elders, Petra J. M.
- Damrauer, Scott M.
- Kivimaki, Mika
- van der Harst, Pim
- Spector, Tim D.
- Loos, Ruth J. F.
- Province, Michael A.
- Psaty, Bruce M.
- Brandslund, Ivan
- Pramstaller, Peter P.
- Christensen, Kaare
- Ripatti, Samuli
- Widén, Elisabeth
- Hakonarson, Hakon
- Grant, Struan F. A.
- Kiemeney, Lambertus A. L. M.
- Loeffler, Markus
- Kronenberg, Florian
- Gu, Dongfeng
- Erdmann, Jeanette
- Schunkert, Heribert
- Franks, Paul W.
- Linneberg, Allan
- Jukema, J. Wouter
- Khera, Amit V.
- Männikkö, Minna
- Cucca, Francesco
- van Dijk, Ko Willems
- Watkins, Hugh
- Strachan, David P.
- Grarup, Niels
- Poulter, Neil
- Rotter, Jerome I.
- Dantoft, Thomas M.
- Karpe, Fredrik
- Neville, Matt J.
- Timpson, Nicholas J.
- Cheng, Ching-Yu
- Wong, Tien-Yin
- Khor, Chiea Chuen
- Sabanayagam, Charumathi
- Peters, Annette
- Gieger, Christian
- Hattersley, Andrew T.
- Pedersen, Nancy L.
- Magnusson, Patrik K. E.
- Boomsma, Dorret I.
- de Geus, Eco J. C.
- Cupples, L. Adrienne
- van Meurs, Joyce B. J.
- Ghanbari, Mohsen
- Gordon-Larsen, Penny
- Huang, Wei
- Kim, Young Jin
- Wareham, Nicholas J.
- Langenberg, Claudia
- Zeggini, Eleftheria
- Kuusisto, Johanna
- Laakso, Markku
- Ingelsson, Erik
- Chambers, John C.
- Kooner, Jaspal S.
- de Vries, Paul S.
- Morrison, Alanna C.
- North, Kari E.
- Daviglus, Martha
- Kraft, Peter
- Martin, Nicholas G.
- Whitfield, John B.
- Saleheen, Danish
- Walters, Robin G.
- Holmes, Michael V.
- Black, Corri
- Smith, Blair H.
- Justice, Anne E.
- Baras, Aris
- Buring, Julie E.
- Ridker, Paul M.
- Chasman, Daniel I.
- Kooperberg, Charles
- Wei, Wei-Qi
- Jarvik, Gail P.
- Namjou, Bahram
- Hayes, M. Geoffrey
- Ritchie, Marylyn D.
- Jousilahti, Pekka
- Salomaa, Veikko
- Hveem, Kristian
- Åsvold, Bjørn Olav
- Kubo, Michiaki
- Okada, Yukinori
- Murakami, Yoshinori
- Ho, Yuk-Lam
- Lynch, Julie A.
- Rader, Daniel J.
- Tsao, Philip S.
- Chang, Kyong-Mi
- Cho, Kelly
- O’Donnell, Christopher J.
- Gaziano, John M.
- Wilson, Peter
- Rotimi, Charles N.
- Hazelhurst, Scott
- Ramsay, Michèle
- Trembath, Richard C.
- van Heel, David A.
- Tamiya, Gen
- Yamamoto, Masayuki
- Kim, Bong-Jo
- Mohlke, Karen L.
- Frayling, Timothy M.
- Hirschhorn, Joel N.
- Kathiresan, Sekar
- Boehnke, Michael
- Natarajan, Pradeep
- Peloso, Gina M.
- Brown, Christopher D.
- Morris, Andrew P.
- Assimes, Themistocles L.
- Deloukas, Panos
- Sun, Yan V.
- Willer, Cristen J.
- Venue
- Nature
- Published
- 2021-12-09
- Volume
- 600
- Issue
- 7890
- Pages
- 675-679
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8730582
- OpenAlex
- W3205644245
- Cited by
- 972
- References
- 77
- Citations by year
- 2026: 164 · 2025: 246 · 2024: 274 · 2023: 192 · 2022: 89 · 2021: 6
- FWCI
- 21.98
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-05-26)
- Open access
- bronze
- doi.org
- Licence
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- Funders
- U.S. Department of Veterans Affairs (IK2-CX001780, I01-BX004821, I01-BX003362)
- McKnight Foundation
- Office of Research and Development
- Wellcome Trust (212946/Z/18/Z, 212945/Z/18/Z, 210561/Z/18/Z, 217065/Z/19/Z, 202802/Z/16/Z, 221854/Z/20/Z)
- Barts Charity (MGU0284)
- Cancer Research UK (16896)
- National Institute for Health and Care Research (NF-SI-0611-10170, NF-SI-0512-10113, NIHR-INF-0987, 16/136/102, NF-SI-0617-10154)
- British Heart Foundation (FS/19/62/34901D, RG/14/5/30893)
- Public Health Agency (STL/5569/19)
- Lundbeckfonden (R155-2013-14070)
- Novo Nordisk Fonden (NNF14OC0010513, NNF19OC0055250, NNF18OC0033898, NNF13OC0005785)
- National Institutes of Health (5k01hl135405-04, 24460, 85,86)
- Medical Research Council (MR/S019669/1, MC_PC_14135, MC_UU_00017/1, MR/S011676/1, MR/R024227/1, MC_PC_15018, MC_PC_20026, MC_PC_19009, MC_UU_00007/10, MC_PC_13049)
- Economic and Social Research Council (ES/N00812X/1, ES/L008459/1)
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- National Institute on Aging (R01AG017917, R01AG015819, P30AG010161)
- National Heart, Lung, and Blood Institute (R01HL133218, R01HL127564, R03HL154284, K01-HL135405, R35HL135818, R01HL149683, R35HL135824, R01HL105756, R01HL109946, R01HL153805)
- National Human Genome Research Institute (K08HG010155, R01HG010297, T32HG000040, U01HG011723)
- National Cancer Institute (R01CA144034, R01CA080205, UM1CA182876)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072193, U01DK062370, P30DK020572, R01DK093757, P30DK020541, R01DK062370)
- National Center for Chronic Disease Prevention and Health Promotion (U01DP006266)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD030880)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- serum lipids, genetic diversity, non-European ancestry, polygenic risk score, fine mapping, cardiovascular risk, LDL cholesterol, triglycerides, HDL cholesterol, genetic ancestry, sample size and statistical power, linkage disequilibrium
- MeSH terms
- Cardiovascular Diseases, Humans, Linkage Disequilibrium, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Population Groups, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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