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AuthorGraham, Sarah E.
AuthorClarke, Shoa L.
AuthorWu, Kuan Han H.
AuthorKanoni, Stavroula
AuthorZajac, Greg J.M.
AuthorRamdas, Shweta
AuthorSurakka, Ida
AuthorNtalla, Ioanna
AuthorVedantam, Sailaja
AuthorWinkler, Thomas W.
AuthorLocke, Adam E.
AuthorMarouli, Eirini
AuthorHwang, Mi Yeong
AuthorHan, Sohee
AuthorNarita, Akira
AuthorChoudhury, Ananyo
AuthorBentley, Amy R.
AuthorEkoru, Kenneth
AuthorVerma, Anurag
AuthorTrivedi, Bhavi
AuthorMartin, Hilary C.
AuthorHunt, Karen A.
AuthorHui, Qin
AuthorKlarin, Derek
AuthorZhu, Xiang
AuthorThorleifsson, Gudmar
AuthorHelgadottir, Anna
AuthorGudbjartsson, Daniel F.
AuthorHolm, Hilma
AuthorOlafsson, Isleifur
AuthorAkiyama, Masato
AuthorSakaue, Saori
AuthorTerao, Chikashi
AuthorKanai, Masahiro
AuthorZhou, Wei
AuthorBrumpton, Ben M.
AuthorRasheed, Humaira
AuthorRuotsalainen, Sanni E.
AuthorHavulinna, Aki S.
AuthorVeturi, Yogasudha
AuthorFeng, Qi Ping
AuthorRosenthal, Elisabeth A.
AuthorLingren, Todd
AuthorPacheco, Jennifer Allen
AuthorPendergrass, Sarah A.
AuthorHaessler, Jeffrey
AuthorGiulianini, Franco
AuthorBradford, Yuki
AuthorMiller, Jason E.
AuthorCampbell, Archie
AuthorLin, Kuang
AuthorMillwood, Iona Y.
AuthorHindy, George
AuthorRasheed, Asif
AuthorFaul, Jessica D.
AuthorZhao, Wei
AuthorWeir, David R.
AuthorTurman, Constance
AuthorHuang, Hongyan
AuthorGraff, Mariaelisa
AuthorMahajan, Anubha
AuthorBrown, Michael R.
AuthorZhang, Weihua
AuthorYu, Ketian
AuthorSchmidt, Ellen M.
AuthorPandit, Anita
AuthorGustafsson, Stefan
AuthorYin, Xianyong
AuthorLuan, Jian’an
AuthorZhao, Jing Hua
AuthorMatsuda, Fumihiko
AuthorJang, Hye Mi
AuthorYoon, Kyungheon
AuthorMedina-Gomez, Carolina
AuthorPitsillides, Achilleas
AuthorHottenga, Jouke Jan
AuthorWillemsen, Gonneke
AuthorWood, Andrew R.
AuthorJi, Yingji
AuthorGao, Zishan
AuthorHaworth, Simon
AuthorMitchell, Ruth E.
AuthorChai, Jin Fang
AuthorAadahl, Mette
AuthorYao, Jie
AuthorManichaikul, Ani
AuthorWarren, Helen R.
AuthorRamirez, Julia
AuthorBork-Jensen, Jette
AuthorKårhus, Line L.
AuthorGoel, Anuj
AuthorSabater-Lleal, Maria
AuthorNoordam, Raymond
AuthorSidore, Carlo
AuthorFiorillo, Edoardo
AuthorMcDaid, Aaron F.
AuthorMarques-Vidal, Pedro
AuthorWielscher, Matthias
AuthorTrompet, Stella
AuthorSattar, Naveed
Available date2023-08-28T10:20:49Z
Publication Date2021-12-23
Publication NameNature
Identifierhttp://dx.doi.org/10.1038/s41586-021-04064-3
CitationGraham, S.E., Clarke, S.L., Wu, KH.H. et al. The power of genetic diversity in genome-wide association studies of lipids. Nature 600, 675–679 (2021). https://doi.org/10.1038/s41586-021-04064-3
ISSN00280836
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85121605114&origin=inward
URIhttp://hdl.handle.net/10576/46845
AbstractIncreased 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.
SponsorFunding for the Global Lipids Genetics Consortium was provided by the NIH (R01-HL127564). This research was conducted using the UK Biobank Resource under application number 24460. Computing support and file management for central meta-analysis by S. Caron is acknowledged. This research is based on data from the MVP, Office of Research and Development, Veterans Health Administration, and was supported by awards 2I01BX003362-03A1 and 1I01BX004821-01A1. This publication does not represent the views of the Department of Veteran Affairs or the United States Government. Study-specific acknowledgements are provided in the Supplementary Information.
Languageen
PublisherNature Research
SubjectComputational models
Genome-wide association studies
Preventive medicine
Risk factors
TitleThe power of genetic diversity in genome-wide association studies of lipids
TypeArticle
Pagination675-679
Issue Number7890
Volume Number600
dc.accessType Abstract Only


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