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Keaton, J.M.* ; Kamali, Z.* ; Xie, T.* ; Vaez, A.* ; Williams, A.* ; Goleva, S.B.* ; Ani, A.* ; Evangelou, E.* ; Hellwege, J.N.* ; Yengo, L.* ; Young, W.J.* ; Traylor, M.* ; Giri, A.* ; Zheng, Z.* ; Zeng, J.* ; Chasman, D.I.* ; Morris, A.P.* ; Caulfield, M.J.* ; Hwang, S.J.* ; Kooner, J.S.* ; Conen, D.* ; Attia, J.R.* ; Morrison, A.C.* ; Loos, R.J.F.* ; Kristiansson, K.* ; Schmidt, R.* ; Hicks, A.A.* ; Pramstaller, P.P.* ; Nelson, C.P.* ; Samani, N.J.* ; Risch, L.* ; Gyllensten, U.* ; Melander, O.* ; Riese, H.* ; Wilson, J.F.* ; Campbell, H.* ; Rich, S.S.* ; Psaty, B.M.* ; Lu, Y.* ; Rotter, J.I.* ; Guo, X.* ; Rice, K.M.* ; Vollenweider, P.* ; Sundström, J.* ; Langenberg, C.* ; Tobin, M.D.* ; Giedraitis, V.* ; Luan, J.* ; Tuomilehto, J.* ; Kutalik, Z.* ; Ripatti, S.* ; Salomaa, V.* ; Girotto, G.* ; Trompet, S.* ; Jukema, J.W.* ; van der Harst, P.* ; Ridker, P.M.* ; Giulianini, F.* ; Vitart, V.* ; Goel, A.* ; Watkins, H.* ; Harris, S.E.* ; Deary, I.J.* ; van der Most, P.J.* ; Oldehinkel, A.J.* ; Keavney, B.D.* ; Hayward, C.* ; Campbell, A.* ; Boehnke, M.* ; Scott, L.J.* ; Boutin, T.* ; Mamasoula, C.* ; Järvelin, M.R.* ; Peters, A. ; Gieger, C. ; Lakatta, E.G.* ; Cucca, F.* ; Hui, J.* ; Knekt, P.* ; Enroth, S.* ; de Borst, M.H.* ; Polašek, O.* ; Concas, M.P.* ; Catamo, E.* ; Cocca, M.* ; Li-Gao, R.* ; Hofer, E.* ; Schmidt, H.* ; Spedicati, B.* ; Waldenberger, M. ; Strachan, D.P.* ; Laan, M.* ; Teumer, A.* ; Dörr, M.* ; Gudnason, V.* ; Cook, J.P.* ; Ruggiero, D.* ; Kolcic, I.* ; Boerwinkle, E.* ; Traglia, M.* ; Lehtimäki, T.* ; Raitakari, O.T.* ; Johnson, A.D.* ; Newton-Cheh, C.* ; Brown, M.J.* ; Dominiczak, A.F.* ; Sever, P.J.* ; Poulter, N.* ; Chambers, J.C.* ; Elosua, R.* ; Siscovick, D.* ; Esko, T.* ; Metspalu, A.* ; Strawbridge, R.J.* ; Laakso, M.* ; Hamsten, A.* ; Hottenga, J.J.* ; de Geus, E.* ; Morris, A.D.* ; Palmer, C.N.A.* ; Nolte, I.M.* ; Milaneschi, Y.* ; Marten, J.* ; Wright, A.* ; Zeggini, E. ; Howson, J.M.M.* ; O'Donnell, C.J.* ; Spector, T.* ; Nalls, M.A.* ; Simonsick, E.M.* ; Liu, Y.* ; van Duijn, C.M.* ; Butterworth, A.S.* ; Danesh, J.N.* ; Menni, C.* ; Wareham, N.J.* ; Khaw, K.T.* ; Sun, Y.V.* ; Wilson, P.W.F.* ; Cho, K.* ; Visscher, P.M.* ; Denny, J.C.* ; Levy, D.* ; Edwards, T.L.* ; Munroe, P.B.* ; Snieder, H.* ; Warren, H.R.*

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

Nat. Genet. 56, 778-791 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Prediction Models; Association; Variants; Hypertension; Loci; Rare; Metaanalysis; Expression; Imputation; Biobank
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 56, Heft: 5, Seiten: 778-791 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Translational Genomics (ITG)
Förderungen Million Veteran Program (MVP) VA Award
National Institute for Health Research Senior Investigator Award
British Heart Foundation Professorship
Iran's National Elites Foundation
Isfahan University of Medical Sciences
Estonian Research Council
Council of Europe
National Institutes of Health