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Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Keaton, Jacob M; Kamali, Zoha; Xie, Tian; Vaez, Ahmad; Williams, Ariel; Goleva, Slavina B; Ani, Alireza; Evangelou, Evangelos; Hellwege, Jacklyn N; Yengo, Loic; Young, William J; Traylor, Matthew; Giri, Ayush; Zheng, Zhili; Zeng, Jian; Chasman, Daniel I; Morris, Andrew P; Caulfield, Mark J; Hwang, Shih-Jen; Kooner, Jaspal S; Conen, David; Attia, John R; Morrison, Alanna C; Loos, Ruth J F; Kristiansson, Kati; Schmidt, Reinhold; Hicks, Andrew A; Pramstaller, Peter P; Nelson, Christopher P; Samani, Nilesh J; Risch, Lorenz; Gyllensten, Ulf; Melander, Olle; Riese, Harriette; Wilson, James F; Campbell, Harry; Rich, Stephen S; Psaty, Bruce M; Lu, Yingchang; Rotter, Jerome I; Guo, Xiuqing; Rice, Kenneth M; Vollenweider, Peter; Sundström, Johan; Langenberg, Claudia; Tobin, Martin D; Giedraitis, Vilmantas; Luan, Jian'an; Tuomilehto, Jaakko; Kutalik, Zoltan.
  • Keaton JM; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Kamali Z; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Xie T; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Vaez A; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Williams A; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Goleva SB; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. a.vaez@umcg.nl.
  • Ani A; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran. a.vaez@umcg.nl.
  • Evangelou E; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Hellwege JN; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Yengo L; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Young WJ; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Traylor M; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Giri A; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
  • Zheng Z; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece.
  • Zeng J; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Chasman DI; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Morris AP; Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.
  • Caulfield MJ; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Hwang SJ; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Kooner JS; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  • Conen D; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Attia JR; Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK.
  • Morrison AC; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Loos RJF; Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Kristiansson K; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Schmidt R; Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Hicks AA; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Pramstaller PP; Division of Preventive Medicine Brigham and Women's Hospital, Boston, MA, USA.
  • Nelson CP; Harvard Medical School, Boston, MA, USA.
  • Samani NJ; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.
  • Risch L; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Gyllensten U; NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Melander O; Population Sciences Branch, NHLBI Framingham Heart Study, Framingham, MA, USA.
  • Riese H; Department of Biostatistics, Boston University, Boston, MA, USA.
  • Wilson JF; National Heart and Lung Institute, Imperial College London, London, UK.
  • Campbell H; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
  • Rich SS; Faculty of Health and Medicine, University of Newcastle, New Lambton Heights, Newcastle, New South Wales, Australia.
  • Psaty BM; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Lu Y; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rotter JI; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Guo X; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Rice KM; Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
  • Vollenweider P; Department of Neurology/Medical University Graz, Graz, Austria.
  • Sundström J; Institute for Biomedicine, Eurac Research, Bolzano, Italy.
  • Langenberg C; University of Lübeck, Lübeck, Germany.
  • Tobin MD; Institute for Biomedicine, Eurac Research, Bolzano, Italy.
  • Giedraitis V; University of Lübeck, Lübeck, Germany.
  • Luan J; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Tuomilehto J; NIHR Leicester Biomedical Research Centre, Leicester, UK.
  • Kutalik Z; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Nat Genet ; 56(5): 778-791, 2024 May.
Article en En | MEDLINE | ID: mdl-38689001
ABSTRACT
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Presión Sanguínea / Predisposición Genética a la Enfermedad / Herencia Multifactorial / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo / Hipertensión Límite: Female / Humans / Male Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Presión Sanguínea / Predisposición Genética a la Enfermedad / Herencia Multifactorial / Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo / Hipertensión Límite: Female / Humans / Male Idioma: En Año: 2024 Tipo del documento: Article