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

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, RJF; 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, CNA; Nolte, I.M.; Milaneschi, Y.; Marten, J.; Wright, A.; Zeggini, E.; Howson, JMM; 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, PWF; Cho, K.; Visscher, P.M.; Denny, J.C.; Levy, D.; Edwards, T.L.; Munroe, P.B.; Snieder, H.; Warren, H.R.

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.

Details

Download: s41588-024-01714-w.pdf (3878.66 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_77928D3D34C1

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

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 RJF, 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 CNA, Nolte I.M., Milaneschi Y., Marten J., Wright A., Zeggini E., Howson JMM, 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 PWF, Cho K., Visscher P.M., Denny J.C., Levy D., Edwards T.L., Munroe P.B., Snieder H., Warren H.R.

Working group(s)

Million Veteran Program, Lifelines Cohort Study, CHARGE consortium, ICBP Consortium

Contributor(s)

van Duijn C.M., Butterworth A.S., Vaez A., Teumer A., Johnson A.D., Morris A.D., Peters A., Goel A., Campbell A., Keavney B.D., Hayward C., Newton-Cheh C., Nelson C.P., Chasman D.I., Levy D., Ruggiero D., de Geus E., Hofer E., Zeggini E., Boerwinkle E., Girotto G., Warren H.R., Watkins H., Kolcic I., Jukema J.W., Hui J., Howson JMM, Sundström J., Chambers J.C., Danesh J.N., Risch L., Caulfield M.J., Laakso M., Tobin M.D., De Borst M.H., Waldenberger M., Samani N.J., Melander O., Raitakari O.T., Polašek O., Munroe P.B., Ridker P.M., van der Harst P., Elosua R., Ripatti S., Lehtimäki T., Young W.J., Kamali Z., Kutalik Z.

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

05/2024

Peer-reviewed

Oui

Volume

Number

Pages

778-791

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

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

Humans, Genome-Wide Association Study, Multifactorial Inheritance/genetics, Blood Pressure/genetics, White People/genetics, Polymorphism, Single Nucleotide, Hypertension/genetics, Genetic Predisposition to Disease, Risk Factors, Male, Female, Genetic Risk Score

URN

urn:nbn:ch:serval-BIB_77928D3D34C18

OAI-PMH

oai:serval.unil.ch:BIB_77928D3D34C1

DOI

10.1038/s41588-024-01714-w

Pubmed

38689001

Web of science

001253620800001

Open Access

Yes