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; Young, William J.; Lehtimäki, T; Raitakari, OT; Johnson, AD; Newton-Cheh, C; Brown, MJ; Dominiczak, AF; Sever, PJ; Poulter, N; Chambers, JC; Elosua, R; Traylor, Matthew; Siscovick, D; Esko, T; Metspalu, A; Strawbridge, RJ; Laakso, M; Hamsten, A; Hottenga, J-J; de Geus, E; Morris, AD; Palmer, CNA; Giri, Ayush; Nolte, IM; Milaneschi, Y; Marten, J; Wright, A; Zeggini, E; Howson, JMM; O'Donnell, CJ; Spector, T; Nalls, MA; Simonsick, EM; Zheng, Zhili; Liu, Y; van Duijn, CM; Butterworth, AS; Danesh, JN; Menni, C; Wareham, NJ; Khaw, K-T; Sun, YV; Wilson, PWF; Cho, K; Zeng, Jian; Visscher, PM; Denny, JC; Million Veteran Program,; Lifelines Cohort Study,; CHARGE consortium,; ICBP Consortium,; Levy, D; Edwards, TL; Munroe, PB; Snieder, H; Chasman, Daniel I.; Warren, HR; Morris, Andrew P.; Caulfield, Mark J.; Hwang, Shih-Jen; Kooner, Jaspal S.; Xie, Tian; Attia, John R.; Attia, JR; Morrison, AC; Loos, RJF; Kristiansson, K; Schmidt, R; Hicks, AA; Pramstaller, PP; Nelson, CP; Samani, NJ; Vaez, Ahmad; Risch, L; Gyllensten, U; Melander, O; Riese, H; Wilson, JF; Campbell, H; Rich, SS; Psaty, BM; Lu, Y; Rotter, JI; Williams, Ariel; Guo, X; Rice, KM; Vollenweider, P; Sundström, J; Langenberg, C; Tobin, MD; Giedraitis, V; Luan, J; Tuomilehto, J; Kutalik, Z; Goleva, Slavina B.; Ripatti, S; Salomaa, V; Girotto, G; Trompet, S; Jukema, JW; van der Harst, P; Ridker, PM; Giulianini, F; Vitart, V; Goel, A; Ani, Alireza; Watkins, H; Harris, SE; Deary, IJ; van der Most, PJ; Oldehinkel, AJ; Keavney, BD; Hayward, C; Campbell, A; Boehnke, M; Scott, LJ; Evangelou, Evangelos; Boutin, T; Mamasoula, C; Järvelin, M-R; Peters, A; Gieger, C; Lakatta, EG; Cucca, F; Hui, J; Knekt, P; Enroth, S; Hellwege, Jacklyn N.; De Borst, MH; Polašek, O; Concas, MP; Catamo, E; Cocca, M; Li-Gao, R; Hofer, E; Schmidt, H; Spedicati, B; Waldenberger, M; Yengo, Loic; Strachan, DP; Laan, M; Teumer, A; Dörr, M; Gudnason, V; Cook, JP; Ruggiero, D; Kolcic, I; Boerwinkle, E; Traglia, M

Title
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Creator
Keaton, Jacob M.; Kamali, Zoha; Young, William J.; Lehtimäki, T; Raitakari, OT; Johnson, AD; Newton-Cheh, C; Brown, MJ; Dominiczak, AF; Sever, PJ; Poulter, N; Chambers, JC; Elosua, R; Traylor, Matthew; Siscovick, D; Esko, T; Metspalu, A; Strawbridge, RJ; Laakso, M; Hamsten, A; Hottenga, J-J; de Geus, E; Morris, AD; Palmer, CNA; Giri, Ayush; Nolte, IM; Milaneschi, Y; Marten, J; Wright, A; Zeggini, E; Howson, JMM; O'Donnell, CJ; Spector, T; Nalls, MA; Simonsick, EM; Zheng, Zhili; Liu, Y; van Duijn, CM; Butterworth, AS; Danesh, JN; Menni, C; Wareham, NJ; Khaw, K-T; Sun, YV; Wilson, PWF; Cho, K; Zeng, Jian; Visscher, PM; Denny, JC; Million Veteran Program,; Lifelines Cohort Study,; CHARGE consortium,; ICBP Consortium,; Levy, D; Edwards, TL; Munroe, PB; Snieder, H; Chasman, Daniel I.; Warren, HR; Morris, Andrew P.; Caulfield, Mark J.; Hwang, Shih-Jen; Kooner, Jaspal S.; Xie, Tian; Attia, John R.; Attia, JR; Morrison, AC; Loos, RJF; Kristiansson, K; Schmidt, R; Hicks, AA; Pramstaller, PP; Nelson, CP; Samani, NJ; Vaez, Ahmad; Risch, L; Gyllensten, U; Melander, O; Riese, H; Wilson, JF; Campbell, H; Rich, SS; Psaty, BM; Lu, Y; Rotter, JI; Williams, Ariel; Guo, X; Rice, KM; Vollenweider, P; Sundström, J; Langenberg, C; Tobin, MD; Giedraitis, V; Luan, J; Tuomilehto, J; Kutalik, Z; Goleva, Slavina B.; Ripatti, S; Salomaa, V; Girotto, G; Trompet, S; Jukema, JW; van der Harst, P; Ridker, PM; Giulianini, F; Vitart, V; Goel, A; Ani, Alireza; Watkins, H; Harris, SE; Deary, IJ; van der Most, PJ; Oldehinkel, AJ; Keavney, BD; Hayward, C; Campbell, A; Boehnke, M; Scott, LJ; Evangelou, Evangelos; Boutin, T; Mamasoula, C; Järvelin, M-R; Peters, A; Gieger, C; Lakatta, EG; Cucca, F; Hui, J; Knekt, P; Enroth, S; Hellwege, Jacklyn N.; De Borst, MH; Polašek, O; Concas, MP; Catamo, E; Cocca, M; Li-Gao, R; Hofer, E; Schmidt, H; Spedicati, B; Waldenberger, M; Yengo, Loic; Strachan, DP; Laan, M; Teumer, A; Dörr, M; Gudnason, V; Cook, JP; Ruggiero, D; Kolcic, I; Boerwinkle, E; Traglia, M
Relation
Nature Genetics Vol. 56, Issue 5, p. 778-791
Publisher Link
http://dx.doi.org/10.1038/s41588-024-01714-w
Publisher
Nature Publishing Group
Resource Type
journal article
Date
2024
Description
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.
Subject
hypertension; metagenomics; genomic studies; predictive models
Identifier
http://hdl.handle.net/1959.13/1503763
Identifier
uon:55383
Identifier
ISSN:1061-4036
Language
eng
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