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المؤلفGraham, Sarah E.
المؤلفClarke, Shoa L.
المؤلفWu, Kuan Han H.
المؤلفKanoni, Stavroula
المؤلفZajac, Greg J.M.
المؤلفRamdas, Shweta
المؤلفSurakka, Ida
المؤلفNtalla, Ioanna
المؤلفVedantam, Sailaja
المؤلفWinkler, Thomas W.
المؤلفLocke, Adam E.
المؤلفMarouli, Eirini
المؤلفHwang, Mi Yeong
المؤلفHan, Sohee
المؤلفNarita, Akira
المؤلفChoudhury, Ananyo
المؤلفBentley, Amy R.
المؤلفEkoru, Kenneth
المؤلفVerma, Anurag
المؤلفTrivedi, Bhavi
المؤلفMartin, Hilary C.
المؤلفHunt, Karen A.
المؤلفHui, Qin
المؤلفKlarin, Derek
المؤلفZhu, Xiang
المؤلفThorleifsson, Gudmar
المؤلفHelgadottir, Anna
المؤلفGudbjartsson, Daniel F.
المؤلفHolm, Hilma
المؤلفOlafsson, Isleifur
المؤلفAkiyama, Masato
المؤلفSakaue, Saori
المؤلفTerao, Chikashi
المؤلفKanai, Masahiro
المؤلفZhou, Wei
المؤلفBrumpton, Ben M.
المؤلفRasheed, Humaira
المؤلفRuotsalainen, Sanni E.
المؤلفHavulinna, Aki S.
المؤلفVeturi, Yogasudha
المؤلفFeng, Qi Ping
المؤلفRosenthal, Elisabeth A.
المؤلفLingren, Todd
المؤلفPacheco, Jennifer Allen
المؤلفPendergrass, Sarah A.
المؤلفHaessler, Jeffrey
المؤلفGiulianini, Franco
المؤلفBradford, Yuki
المؤلفMiller, Jason E.
المؤلفCampbell, Archie
المؤلفLin, Kuang
المؤلفMillwood, Iona Y.
المؤلفHindy, George
المؤلفRasheed, Asif
المؤلفFaul, Jessica D.
المؤلفZhao, Wei
المؤلفWeir, David R.
المؤلفTurman, Constance
المؤلفHuang, Hongyan
المؤلفGraff, Mariaelisa
المؤلفMahajan, Anubha
المؤلفBrown, Michael R.
المؤلفZhang, Weihua
المؤلفYu, Ketian
المؤلفSchmidt, Ellen M.
المؤلفPandit, Anita
المؤلفGustafsson, Stefan
المؤلفYin, Xianyong
المؤلفLuan, Jian’an
المؤلفZhao, Jing Hua
المؤلفMatsuda, Fumihiko
المؤلفJang, Hye Mi
المؤلفYoon, Kyungheon
المؤلفMedina-Gomez, Carolina
المؤلفPitsillides, Achilleas
المؤلفHottenga, Jouke Jan
المؤلفWillemsen, Gonneke
المؤلفWood, Andrew R.
المؤلفJi, Yingji
المؤلفGao, Zishan
المؤلفHaworth, Simon
المؤلفMitchell, Ruth E.
المؤلفChai, Jin Fang
المؤلفAadahl, Mette
المؤلفYao, Jie
المؤلفManichaikul, Ani
المؤلفWarren, Helen R.
المؤلفRamirez, Julia
المؤلفBork-Jensen, Jette
المؤلفKårhus, Line L.
المؤلفGoel, Anuj
المؤلفSabater-Lleal, Maria
المؤلفNoordam, Raymond
المؤلفSidore, Carlo
المؤلفFiorillo, Edoardo
المؤلفMcDaid, Aaron F.
المؤلفMarques-Vidal, Pedro
المؤلفWielscher, Matthias
المؤلفTrompet, Stella
المؤلفSattar, Naveed
تاريخ الإتاحة2023-08-28T10:20:49Z
تاريخ النشر2021-12-23
اسم المنشورNature
المعرّفhttp://dx.doi.org/10.1038/s41586-021-04064-3
الاقتباسGraham, 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
الرقم المعياري الدولي للكتاب00280836
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85121605114&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/46845
الملخصIncreased 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.
راعي المشروعFunding 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.
اللغةen
الناشرNature Research
الموضوعComputational models
Genome-wide association studies
Preventive medicine
Risk factors
العنوانThe power of genetic diversity in genome-wide association studies of lipids
النوعArticle
الصفحات675-679
رقم العدد7890
رقم المجلد600
dc.accessType Abstract Only


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