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

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 P. 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; Million Veteran Program; Lifelines Cohort Study; CHARGE consortium; ICBP Consortium; Daniel Levy; Todd L. Edwards; Patricia B. Munroe; Harold Snieder; Helen R. Warren

doi:10.1038/s41588-024-01714-w

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

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. KoonerDavid 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 P. 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, Million Veteran Program, Lifelines Cohort Study, CHARGE consortium, ICBP Consortium, Daniel Levy, Todd L. Edwards, Patricia B. Munroe, Harold Snieder, Helen R. Warren

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	778-791
Number of pages	14
Journal	Nature Genetics
Volume	56
Issue number	5
Early online date	30 Apr 2024
DOIs	https://doi.org/10.1038/s41588-024-01714-w
Publication status	Published - May 2024

Keywords / Materials (for Non-textual outputs)

hypertension
metagenomics

Access to Document

10.1038/s41588-024-01714-wLicence: Creative Commons: Attribution (CC-BY)

KeatonEtalNG2024Genome-wideAnalysisFinal published version, 3.79 MBLicence: Creative Commons: Attribution (CC-BY)

http://www.doi.org.uk/10.1038/s41588-024-01714-wLicence: Creative Commons: Attribution (CC-BY)

Cite this

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., ... Warren, H. R. (2024). Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nature Genetics, 56(5), 778-791. https://doi.org/10.1038/s41588-024-01714-w

@article{df4eb76357964b7a8eef5d7422483a04,

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

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.",

keywords = "hypertension, metagenomics",

author = "Keaton, {Jacob M.} and Zoha Kamali and Tian Xie and Ahmad Vaez and Ariel Williams and Goleva, {Slavina B.} and Alireza Ani and Evangelos Evangelou and Hellwege, {Jacklyn N.} and Loic Yengo and Young, {William J.} and Matthew Traylor and Ayush Giri and Zhili Zheng and Jian Zeng and Chasman, {Daniel I.} and Morris, {Andrew P.} and Caulfield, {Mark J.} and Shih-Jen Hwang and Kooner, {Jaspal S.} and David Conen and Attia, {John R.} and Morrison, {Alanna C.} and Loos, {Ruth J. F.} and Kati Kristiansson and Reinhold Schmidt and Hicks, {Andrew A.} and Pramstaller, {Peter P.} and Nelson, {Christopher P.} and Samani, {Nilesh J.} and Lorenz Risch and Ulf Gyllensten and Olle Melander and Harriette Riese and Wilson, {James F.} and Harry Campbell and Rich, {Stephen S.} and Psaty, {Bruce M.} and Yingchang Lu and Rotter, {Jerome I.} and Xiuqing Guo and Rice, {Kenneth M.} and Peter Vollenweider and Johan Sundstr{\"o}m and Claudia Langenberg and Tobin, {Martin D.} and Vilmantas Giedraitis and Jian{\textquoteright}an Luan and Jaakko Tuomilehto and Zoltan Kutalik and Samuli Ripatti and Veikko Salomaa and Giorgia Girotto and Stella Trompet and Jukema, {J. Wouter} and {van der Harst}, Pim and Ridker, {Paul M.} and Franco Giulianini and Veronique Vitart and Anuj Goel and Hugh Watkins and Harris, {Sarah E.} and Deary, {Ian J.} and {van der Most}, {Peter J.} and Oldehinkel, {Albertine J.} and Keavney, {Bernard D.} and Caroline Hayward and Archie Campbell and Michael Boehnke and Scott, {Laura J.} and Thibaud Boutin and Chrysovalanto Mamasoula and Marjo-Riitta J{\"a}rvelin and Annette Peters and Christian Gieger and Lakatta, {Edward G.} and Francesco Cucca and Jennie Hui and Paul Knekt and Stefan Enroth and {De Borst}, {Martin H.} and Ozren Pola{\v s}ek and Concas, {Maria Pina} and Eulalia Catamo and Massimiliano Cocca and Ruifang Li-Gao and Edith Hofer and Helena Schmidt and Beatrice Spedicati and Melanie Waldenberger and Strachan, {David P.} and Maris Laan and Alexander Teumer and Marcus D{\"o}rr and Vilmundur Gudnason and Cook, {James P.} and Daniela Ruggiero and Ivana Kolcic and Eric Boerwinkle and Michela Traglia and Terho Lehtim{\"a}ki and Raitakari, {Olli T.} and Johnson, {Andrew D.} and Christopher Newton-Cheh and Brown, {Morris J.} and Dominiczak, {Anna F.} and Sever, {Peter J.} and Neil Poulter and Chambers, {John C.} and Roberto Elosua and David Siscovick and T{\~o}nu Esko and Andres Metspalu and Strawbridge, {Rona J.} and Markku Laakso and Anders Hamsten and Jouke-Jan Hottenga and {de Geus}, Eco and Morris, {Andrew P.} and Palmer, {Colin N. A.} and Nolte, {Ilja M.} and Yuri Milaneschi and Jonathan Marten and Alan Wright and Eleftheria Zeggini and Howson, {Joanna M. M.} and O{\textquoteright}Donnell, {Christopher J.} and Tim Spector and Nalls, {Mike A.} and Simonsick, {Eleanor M.} and Yongmei Liu and {van Duijn}, {Cornelia M.} and Butterworth, {Adam S.} and Danesh, {John N.} and Cristina Menni and Wareham, {Nicholas J.} and Kay-Tee Khaw and Sun, {Yan V.} and Wilson, {Peter W. F.} and Kelly Cho and Visscher, {Peter M.} and Denny, {Joshua C.} and Program, {Million Veteran} and Study, {Lifelines Cohort} and CHARGE consortium and ICBP Consortium and Daniel Levy and Edwards, {Todd L.} and Munroe, {Patricia B.} and Harold Snieder and Warren, {Helen R.}",

note = "J.M.K., Z.K., T.X., A.V., A. Williams, S.B.G., A.A., E.E., J.N.H. and H.R.W. analyzed the data. J.M.K., Z.K., T.X., A.V., A.A., Z.Z., J.Z., E.E., J.N.H., J.C.D., D.L., T.L.E., P.B.M., H. Snieder and H.R.W. wrote the first draft of the paper. J.M.K., Z. Kutalik, T.X., A.V., A.A., Z.Z., J.Z., E.E., J.N.H., L.Y., W.J.Y., M. Traylor, A. Giri, P.M.V., D.I.C., A.P.M., M.J.C., S.H., J.S.K., D.C., J.R.A., A.C.M., R.J.L., K.K., R.S., A.A.H., P.P.P., C.P.N., N.J.S., L.R., U.G., O.M., H.R., J.F.W., H.C., B.M.P., Y.L., J.I.R., X.G., K.M.R., P.V., J.S., C.L., M.D.T., V. Giedraitis, J.L., J.T., Z.K., S.R., V.S., G.G., S.T., J.W.J., P.v.d.H., P.M.R., F.G., V.V., A. Goel, H.W., S.E.H., I.J.D., P.J.v.d.M., A.J.O., B.D.K., C.H., A.C., M.B., L.J.S., T.B., C. Mamasoula, M.J., A.P., C.G., E.G.L., F.C., J.H., P.K., S.E., M.H.D., O.P., M.P.C., E.C., M.C., R.L., E.H., H. Schmidt, B.S., M.W., D.P.S., M. Laan, A.T., M.D., V. Gudnason, J.P.C., D.R., I.K., E.B., M. Traglia, T.L., O.T.R., A.D.J., C.N., M.J.B., A.F.D., P.J.S., N.P., J.C.C., R.E., D.S., T.E., A.M., R.J.S., M. Laakso, A.H., J.H., E.d.G., A.D.M., C.N.P., I.M.N., Y.M., J.M., A. Wright, E.Z., J.M.H., C.J.O., T.S., M.A.N., E.M.S., Y.L., C.M.v.D., A.S.B., J.N.D., C. Menni, N.J.W., K.K., J.C.D., D.L., T.L.E., P.B.M., H. Snieder and H.R.W. edited the paper. D.L., T.L.E., P.B.M., H. Snieder and H.R.W. led and supervised the project.",

year = "2024",

month = may,

doi = "10.1038/s41588-024-01714-w",

language = "English",

volume = "56",

pages = "778--791",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Publishing Group",

number = "5",

}

Keaton, JM, Kamali, Z, Xie, T, Vaez, A, Williams, A, Goleva, SB, Ani, A, Evangelou, E, Hellwege, JN, Yengo, L, Young, WJ, Traylor, M, Giri, A, Zheng, Z, Zeng, J, Chasman, DI, Morris, AP, Caulfield, MJ, Hwang, S-J, Kooner, JS, Conen, D, Attia, JR, Morrison, AC, Loos, RJF, Kristiansson, K, Schmidt, R, Hicks, AA, Pramstaller, PP, Nelson, CP, Samani, NJ, Risch, L, Gyllensten, U, Melander, O, Riese, H, Wilson, JF , Campbell, H, Rich, SS, Psaty, BM, Lu, Y, Rotter, JI, Guo, X, Rice, KM, Vollenweider, P, Sundström, J, Langenberg, C, Tobin, MD, Giedraitis, V, Luan, J, Tuomilehto, J, Kutalik, Z, Ripatti, S, Salomaa, V, Girotto, G, Trompet, S, Jukema, JW, van der Harst, P, Ridker, PM, Giulianini, F, Vitart, V, Goel, A, Watkins, H, Harris, SE , Deary, IJ, van der Most, PJ, Oldehinkel, AJ, Keavney, BD, Hayward, C , Campbell, A, Boehnke, M, Scott, LJ, Boutin, T, Mamasoula, C, Järvelin, M-R, Peters, A, Gieger, C, Lakatta, EG, Cucca, F, Hui, J, Knekt, P, Enroth, S, De Borst, MH, Polašek, O, Concas, MP, Catamo, E, Cocca, M, Li-Gao, R, Hofer, E, Schmidt, H, Spedicati, B, Waldenberger, M, Strachan, DP, Laan, M, Teumer, A, Dörr, M, Gudnason, V, Cook, JP, Ruggiero, D, Kolcic, I, Boerwinkle, E, Traglia, M, Lehtimäki, T, Raitakari, OT, Johnson, AD, Newton-Cheh, C, Brown, MJ, Dominiczak, AF, Sever, PJ, Poulter, N, Chambers, JC, Elosua, R, Siscovick, D, Esko, T, Metspalu, A, Strawbridge, RJ, Laakso, M, Hamsten, A, Hottenga, J-J, de Geus, E, Morris, AP, Palmer, CNA, Nolte, IM, Milaneschi, Y, Marten, J, Wright, A, Zeggini, E, Howson, JMM, O’Donnell, CJ, Spector, T, Nalls, MA, Simonsick, EM, Liu, Y, van Duijn, CM, Butterworth, AS, Danesh, JN, Menni, C, Wareham, NJ, Khaw, K-T, Sun, YV, Wilson, PWF, Cho, K, Visscher, PM, Denny, JC, Program, MV, Study, LC, consortium, CHARGE, Consortium, ICBP, Levy, D, Edwards, TL, Munroe, PB, Snieder, H & Warren, HR 2024, 'Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits', Nature Genetics, vol. 56, no. 5, pp. 778-791. https://doi.org/10.1038/s41588-024-01714-w

TY - JOUR

T1 - Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

AU - Keaton, Jacob M.

AU - Kamali, Zoha

AU - Xie, Tian

AU - Vaez, Ahmad

AU - Williams, Ariel

AU - Goleva, Slavina B.

AU - Ani, Alireza

AU - Evangelou, Evangelos

AU - Hellwege, Jacklyn N.

AU - Yengo, Loic

AU - Young, William J.

AU - Traylor, Matthew

AU - Giri, Ayush

AU - Zheng, Zhili

AU - Zeng, Jian

AU - Chasman, Daniel I.

AU - Morris, Andrew P.

AU - Caulfield, Mark J.

AU - Hwang, Shih-Jen

AU - Kooner, Jaspal S.

AU - Conen, David

AU - Attia, John R.

AU - Morrison, Alanna C.

AU - Loos, Ruth J. F.

AU - Kristiansson, Kati

AU - Schmidt, Reinhold

AU - Hicks, Andrew A.

AU - Pramstaller, Peter P.

AU - Nelson, Christopher P.

AU - Samani, Nilesh J.

AU - Risch, Lorenz

AU - Gyllensten, Ulf

AU - Melander, Olle

AU - Riese, Harriette

AU - Wilson, James F.

AU - Campbell, Harry

AU - Rich, Stephen S.

AU - Psaty, Bruce M.

AU - Lu, Yingchang

AU - Rotter, Jerome I.

AU - Guo, Xiuqing

AU - Rice, Kenneth M.

AU - Vollenweider, Peter

AU - Sundström, Johan

AU - Langenberg, Claudia

AU - Tobin, Martin D.

AU - Giedraitis, Vilmantas

AU - Luan, Jian’an

AU - Tuomilehto, Jaakko

AU - Kutalik, Zoltan

AU - Ripatti, Samuli

AU - Salomaa, Veikko

AU - Girotto, Giorgia

AU - Trompet, Stella

AU - Jukema, J. Wouter

AU - van der Harst, Pim

AU - Ridker, Paul M.

AU - Giulianini, Franco

AU - Vitart, Veronique

AU - Goel, Anuj

AU - Watkins, Hugh

AU - Harris, Sarah E.

AU - Deary, Ian J.

AU - van der Most, Peter J.

AU - Oldehinkel, Albertine J.

AU - Keavney, Bernard D.

AU - Hayward, Caroline

AU - Campbell, Archie

AU - Boehnke, Michael

AU - Scott, Laura J.

AU - Boutin, Thibaud

AU - Mamasoula, Chrysovalanto

AU - Järvelin, Marjo-Riitta

AU - Peters, Annette

AU - Gieger, Christian

AU - Lakatta, Edward G.

AU - Cucca, Francesco

AU - Hui, Jennie

AU - Knekt, Paul

AU - Enroth, Stefan

AU - De Borst, Martin H.

AU - Polašek, Ozren

AU - Concas, Maria Pina

AU - Catamo, Eulalia

AU - Cocca, Massimiliano

AU - Li-Gao, Ruifang

AU - Hofer, Edith

AU - Schmidt, Helena

AU - Spedicati, Beatrice

AU - Waldenberger, Melanie

AU - Strachan, David P.

AU - Laan, Maris

AU - Teumer, Alexander

AU - Dörr, Marcus

AU - Gudnason, Vilmundur

AU - Cook, James P.

AU - Ruggiero, Daniela

AU - Kolcic, Ivana

AU - Boerwinkle, Eric

AU - Traglia, Michela

AU - Lehtimäki, Terho

AU - Raitakari, Olli T.

AU - Johnson, Andrew D.

AU - Newton-Cheh, Christopher

AU - Brown, Morris J.

AU - Dominiczak, Anna F.

AU - Sever, Peter J.

AU - Poulter, Neil

AU - Chambers, John C.

AU - Elosua, Roberto

AU - Siscovick, David

AU - Esko, Tõnu

AU - Metspalu, Andres

AU - Strawbridge, Rona J.

AU - Laakso, Markku

AU - Hamsten, Anders

AU - Hottenga, Jouke-Jan

AU - de Geus, Eco

AU - Morris, Andrew P.

AU - Palmer, Colin N. A.

AU - Nolte, Ilja M.

AU - Milaneschi, Yuri

AU - Marten, Jonathan

AU - Wright, Alan

AU - Zeggini, Eleftheria

AU - Howson, Joanna M. M.

AU - O’Donnell, Christopher J.

AU - Spector, Tim

AU - Nalls, Mike A.

AU - Simonsick, Eleanor M.

AU - Liu, Yongmei

AU - van Duijn, Cornelia M.

AU - Butterworth, Adam S.

AU - Danesh, John N.

AU - Menni, Cristina

AU - Wareham, Nicholas J.

AU - Khaw, Kay-Tee

AU - Sun, Yan V.

AU - Wilson, Peter W. F.

AU - Cho, Kelly

AU - Visscher, Peter M.

AU - Denny, Joshua C.

AU - Program, Million Veteran

AU - Study, Lifelines Cohort

AU - consortium, CHARGE

AU - Consortium, ICBP

AU - Levy, Daniel

AU - Edwards, Todd L.

AU - Munroe, Patricia B.

AU - Snieder, Harold

AU - Warren, Helen R.

N1 - J.M.K., Z.K., T.X., A.V., A. Williams, S.B.G., A.A., E.E., J.N.H. and H.R.W. analyzed the data. J.M.K., Z.K., T.X., A.V., A.A., Z.Z., J.Z., E.E., J.N.H., J.C.D., D.L., T.L.E., P.B.M., H. Snieder and H.R.W. wrote the first draft of the paper. J.M.K., Z. Kutalik, T.X., A.V., A.A., Z.Z., J.Z., E.E., J.N.H., L.Y., W.J.Y., M. Traylor, A. Giri, P.M.V., D.I.C., A.P.M., M.J.C., S.H., J.S.K., D.C., J.R.A., A.C.M., R.J.L., K.K., R.S., A.A.H., P.P.P., C.P.N., N.J.S., L.R., U.G., O.M., H.R., J.F.W., H.C., B.M.P., Y.L., J.I.R., X.G., K.M.R., P.V., J.S., C.L., M.D.T., V. Giedraitis, J.L., J.T., Z.K., S.R., V.S., G.G., S.T., J.W.J., P.v.d.H., P.M.R., F.G., V.V., A. Goel, H.W., S.E.H., I.J.D., P.J.v.d.M., A.J.O., B.D.K., C.H., A.C., M.B., L.J.S., T.B., C. Mamasoula, M.J., A.P., C.G., E.G.L., F.C., J.H., P.K., S.E., M.H.D., O.P., M.P.C., E.C., M.C., R.L., E.H., H. Schmidt, B.S., M.W., D.P.S., M. Laan, A.T., M.D., V. Gudnason, J.P.C., D.R., I.K., E.B., M. Traglia, T.L., O.T.R., A.D.J., C.N., M.J.B., A.F.D., P.J.S., N.P., J.C.C., R.E., D.S., T.E., A.M., R.J.S., M. Laakso, A.H., J.H., E.d.G., A.D.M., C.N.P., I.M.N., Y.M., J.M., A. Wright, E.Z., J.M.H., C.J.O., T.S., M.A.N., E.M.S., Y.L., C.M.v.D., A.S.B., J.N.D., C. Menni, N.J.W., K.K., J.C.D., D.L., T.L.E., P.B.M., H. Snieder and H.R.W. edited the paper. D.L., T.L.E., P.B.M., H. Snieder and H.R.W. led and supervised the project.

PY - 2024/5

Y1 - 2024/5

N2 - 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.

AB - 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.

KW - hypertension

KW - metagenomics

UR - http://www.ebi.ac.uk/gwas

UR - http://www.pgscatalog.org

U2 - 10.1038/s41588-024-01714-w

DO - 10.1038/s41588-024-01714-w

M3 - Article

C2 - 38689001

SN - 1546-1718

VL - 56

SP - 778

EP - 791

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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