PuSH - Publication Server of Helmholtz Zentrum München: Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

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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)

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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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