ScholarLink (思领科)
错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2024年4月30日

查看全文
  • Jacob M. Keaton,
  • Zoha Kamali,
  • Tian Xie,
  • Ahmad Vaez,
  • Ariel Williams,
  • Slavina B. Goleva,
  • Alireza Ani,
  • Evangelos Evangelou,
  • Jacklyn N. Hellwege,
  • Loic Yengo,
  • William J. Young,
  • Matthew Traylor,
  • Ayush Giri,
  • Zhili Zheng,
  • Jian Zeng,
  • Daniel I. Chasman,
  • Andrew P. Morris,
  • Mark J. Caulfield,
  • Shih-Jen Hwang,
  • Jaspal S. Kooner,
  • David Conen,
  • John R. Attia,
  • Alanna C. Morrison,
  • Ruth J. F. Loos,
  • Kati Kristiansson,
  • Reinhold Schmidt,
  • Andrew A. Hicks,
  • Peter P. Pramstaller,
  • Christopher P. Nelson,
  • Nilesh J. Samani,
  • Lorenz Risch,
  • Ulf Gyllensten,
  • Olle Melander,
  • Harriette Riese,
  • James F. Wilson,
  • Harry Campbell,
  • Stephen S. Rich,
  • Bruce M. Psaty,
  • Yingchang Lu,
  • Jerome I. Rotter,
  • Xiuqing Guo,
  • Kenneth M. Rice,
  • Peter Vollenweider,
  • Johan Sundström,
  • Claudia Langenberg,
  • Martin D. Tobin,
  • Vilmantas Giedraitis,
  • Jian’an Luan,
  • Jaakko Tuomilehto,
  • Zoltan Kutalik,
  • Samuli Ripatti,
  • Veikko Salomaa,
  • Giorgia Girotto,
  • Stella Trompet,
  • J. Wouter Jukema,
  • Pim van der Harst,
  • Paul M. Ridker,
  • Franco Giulianini,
  • Veronique Vitart,
  • Anuj Goel,
  • Hugh Watkins,
  • Sarah E. Harris,
  • Ian J. Deary,
  • Peter J. van der Most,
  • Albertine J. Oldehinkel,
  • Bernard D. Keavney,
  • Caroline Hayward,
  • Archie Campbell,
  • Michael Boehnke,
  • Laura J. Scott,
  • Thibaud Boutin,
  • Chrysovalanto Mamasoula,
  • Marjo-Riitta Järvelin,
  • Annette Peters,
  • Christian Gieger,
  • Edward G. Lakatta,
  • Francesco Cucca,
  • Jennie Hui,
  • Paul Knekt,
  • Stefan Enroth,
  • Martin H. De Borst,
  • Ozren Polašek,
  • Maria Pina Concas,
  • Eulalia Catamo,
  • Massimiliano Cocca,
  • Ruifang Li-Gao,
  • Edith Hofer,
  • Helena Schmidt,
  • Beatrice Spedicati,
  • Melanie Waldenberger,
  • David P. Strachan,
  • Maris Laan,
  • Alexander Teumer,
  • Marcus Dörr,
  • Vilmundur Gudnason,
  • James P. Cook,
  • Daniela Ruggiero,
  • Ivana Kolcic,
  • Eric Boerwinkle,
  • Michela Traglia,
  • Terho Lehtimäki,
  • Olli T. Raitakari,
  • Andrew D. Johnson,
  • Christopher Newton-Cheh,
  • Morris J. Brown,
  • Anna F. Dominiczak,
  • Peter J. Sever,
  • Neil Poulter,
  • John C. Chambers,
  • Roberto Elosua,
  • David Siscovick,
  • Tõnu Esko,
  • Andres Metspalu,
  • Rona J. Strawbridge,
  • Markku Laakso,
  • Anders Hamsten,
  • Jouke-Jan Hottenga,
  • Eco de Geus,
  • Andrew D. Morris,
  • Colin N. A. Palmer,
  • Ilja M. Nolte,
  • Yuri Milaneschi,
  • Jonathan Marten,
  • Alan Wright,
  • Eleftheria Zeggini,
  • Joanna M. M. Howson,
  • Christopher J. O’Donnell,
  • Tim Spector,
  • Mike A. Nalls,
  • Eleanor M. Simonsick,
  • Yongmei Liu,
  • Cornelia M. van Duijn,
  • Adam S. Butterworth,
  • John N. Danesh,
  • Cristina Menni,
  • Nicholas J. Wareham,
  • Kay-Tee Khaw,
  • Yan V. Sun,
  • Peter W. F. Wilson,
  • Kelly Cho,
  • Peter M. Visscher,
  • Joshua C. Denny,
  • Cornelia M. van Duijn,
  • Adam S. Butterworth,
  • Ahmad Vaez,
  • Alexander Teumer,
  • Andrew D. Johnson,
  • Andrew D. Morris,
  • Annette Peters,
  • Anuj Goel,
  • Archie Campbell,
  • Bernard D. Keavney,
  • Caroline Hayward,
  • Christopher Newton-Cheh,
  • Christopher P. Nelson,
  • Daniel I. Chasman,
  • Daniel Levy,
  • Daniela Ruggiero,
  • Eco de Geus,
  • Edith Hofer,
  • Eleftheria Zeggini,
  • Eric Boerwinkle,
  • Giorgia Girotto,
  • Helen R. Warren,
  • Hugh Watkins,
  • Ivana Kolcic,
  • J. Wouter Jukema,
  • Jennie Hui,
  • Joanna M. M. Howson,
  • Johan Sundström,
  • John C. Chambers,
  • John N. Danesh,
  • Lorenz Risch,
  • Mark J. Caulfield,
  • Markku Laakso,
  • Martin D. Tobin,
  • Martin H. De Borst,
  • Melanie Waldenberger,
  • Nilesh J. Samani,
  • Olle Melander,
  • Olli T. Raitakari,
  • Ozren Polašek,
  • Patricia B. Munroe,
  • Paul M. Ridker,
  • Pim van der Harst,
  • Roberto Elosua,
  • Samuli Ripatti,
  • Terho Lehtimäki,
  • William J. Young,
  • Zoha Kamali,
  • Zoltan Kutalik,
  • Daniel Levy,
  • Todd L. Edwards,
  • Patricia B. Munroe,
  • Harold Snieder,
  • Helen R. Warren

摘要

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5–18.2 mmHg, P = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54–9.70; P = 4.13 × 10−44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 0.035, P = 1.98 × 10−34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.