Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Helen R Warren; Evangelos Evangelou; Claudia P Cabrera; He Gao; Meixia Ren; Borbala Mifsud; Ioanna Ntalla; Praveen Surendran; Chunyu Liu; James P Cook; Aldi T Kraja; Fotios Drenos; Marie Loh; Niek Verweij; Jonathan Marten; Ibrahim Karaman; Marcelo P Segura Lepe; Paul F O'Reilly; Joanne Knight; Harold Snieder; Norihiro Kato; Jiang He; E Shyong Tai; M Abdullah Said; David Porteous; Maris Alver; Neil Poulter; Martin Farrall; Ron T Gansevoort; Sandosh Padmanabhan; Reedik Mägi; Alice Stanton; John Connell; Stephan J L Bakker; Andres Metspalu; Denis C Shields; Simon Thom; Morris Brown; Peter Sever; Tõnu Esko; Caroline Hayward; Pim van der Harst; Danish Saleheen; Rajiv Chowdhury; John C Chambers; Daniel I Chasman; International Consortium of Blood Pressure (ICBP) 1000G Analyses; J.J. Hottenga; Eco  de Geus; Gonneke Willemsen; D.I. Boomsma

doi:10.1038/ng.3768

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Helen R Warren, Evangelos Evangelou, Claudia P Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu Liu, James P Cook, Aldi T Kraja, Fotios Drenos, Marie Loh, Niek Verweij, Jonathan Marten, Ibrahim Karaman, Marcelo P Segura Lepe, Paul F O'Reilly, Joanne Knight, Harold SniederNorihiro Kato, Jiang He, E Shyong Tai, M Abdullah Said, David Porteous, Maris Alver, Neil Poulter, Martin Farrall, Ron T Gansevoort, Sandosh Padmanabhan, Reedik Mägi, Alice Stanton, John Connell, Stephan J L Bakker, Andres Metspalu, Denis C Shields, Simon Thom, Morris Brown, Peter Sever, Tõnu Esko, Caroline Hayward, Pim van der Harst, Danish Saleheen, Rajiv Chowdhury, John C Chambers, Daniel I Chasman, International Consortium of Blood Pressure (ICBP) 1000G Analyses, J.J. Hottenga, Eco de Geus, Gonneke Willemsen, D.I. Boomsma

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Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Original language	English
Pages (from-to)	403-415
Number of pages	13
Journal	Nature Genetics
Volume	49
Issue number	3
Early online date	30 Jan 2017
DOIs	https://doi.org/10.1038/ng.3768
Publication status	Published - Mar 2017

Funding

Funders	Funder number
National Heart, Lung, and Blood Institute	R01HL086694

Keywords

Journal Article

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.3768

ng.3768_Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular riskFinal published version, 1.92 MBLicence: Article 25fa Dutch Copyright Act

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Warren, H. R., Evangelou, E., Cabrera, C. P., Gao, H., Ren, M., Mifsud, B., Ntalla, I., Surendran, P., Liu, C., Cook, J. P., Kraja, A. T., Drenos, F., Loh, M., Verweij, N., Marten, J., Karaman, I., Lepe, M. P. S., O'Reilly, P. F., Knight, J., ... Boomsma, D. I. (2017). Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature Genetics, 49(3), 403-415. https://doi.org/10.1038/ng.3768

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abstract = "Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.",

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Warren, HR, Evangelou, E, Cabrera, CP, Gao, H, Ren, M, Mifsud, B, Ntalla, I, Surendran, P, Liu, C, Cook, JP, Kraja, AT, Drenos, F, Loh, M, Verweij, N, Marten, J, Karaman, I, Lepe, MPS, O'Reilly, PF, Knight, J, Snieder, H, Kato, N, He, J, Tai, ES, Said, MA, Porteous, D, Alver, M, Poulter, N, Farrall, M, Gansevoort, RT, Padmanabhan, S, Mägi, R, Stanton, A, Connell, J, Bakker, SJL, Metspalu, A, Shields, DC, Thom, S, Brown, M, Sever, P, Esko, T, Hayward, C, van der Harst, P, Saleheen, D, Chowdhury, R, Chambers, JC, Chasman, DI, International Consortium of Blood Pressure (ICBP) 1000G Analyses, Hottenga, JJ , de Geus, E, Willemsen, G & Boomsma, DI 2017, 'Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk', Nature Genetics, vol. 49, no. 3, pp. 403-415. https://doi.org/10.1038/ng.3768

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AU - Warren, Helen R

AU - Evangelou, Evangelos

AU - Cabrera, Claudia P

AU - Gao, He

AU - Ren, Meixia

AU - Mifsud, Borbala

AU - Ntalla, Ioanna

AU - Surendran, Praveen

AU - Liu, Chunyu

AU - Cook, James P

AU - Kraja, Aldi T

AU - Drenos, Fotios

AU - Loh, Marie

AU - Verweij, Niek

AU - Marten, Jonathan

AU - Karaman, Ibrahim

AU - Lepe, Marcelo P Segura

AU - O'Reilly, Paul F

AU - Knight, Joanne

AU - Snieder, Harold

AU - Kato, Norihiro

AU - He, Jiang

AU - Tai, E Shyong

AU - Said, M Abdullah

AU - Porteous, David

AU - Alver, Maris

AU - Poulter, Neil

AU - Farrall, Martin

AU - Gansevoort, Ron T

AU - Padmanabhan, Sandosh

AU - Mägi, Reedik

AU - Stanton, Alice

AU - Connell, John

AU - Bakker, Stephan J L

AU - Metspalu, Andres

AU - Shields, Denis C

AU - Thom, Simon

AU - Brown, Morris

AU - Sever, Peter

AU - Esko, Tõnu

AU - Hayward, Caroline

AU - van der Harst, Pim

AU - Saleheen, Danish

AU - Chowdhury, Rajiv

AU - Chambers, John C

AU - Chasman, Daniel I

AU - International Consortium of Blood Pressure (ICBP) 1000G Analyses

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AU - Willemsen, Gonneke

AU - Boomsma, D.I.

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AB - Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Abstract

Funding

Keywords

Cohort Studies

UN SDGs

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