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; Aravinda Chakravarti; Christopher Newton-Cheh; Cecilia M. Lindgren; Daniel Levy; Jaspal S. Kooner; Bernard Keavney; Maciej Tomaszewski; Nilesh J. Samani; Joanna M. M. Howson; Martin D. Tobin; Patricia B. Munroe; Georg B. Ehret; Louise V. Wain; Alan J. Gow; The International Consortium of Blood Pressure (ICBP) 1000G Analyses; The CHD Exome+ Consortium; The ExomeBP Consortium; The T2D-GENES Consortium; The GoT2DGenes Consortium; The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium; The International Genomics of Blood Pressure (iGEN -BP) Consortium; for The UK Biobank CardioMetabolic Consortium BP working group Louise

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, Aravinda Chakravarti, Christopher Newton-Cheh, Cecilia M. Lindgren, Daniel Levy, Jaspal S. Kooner, Bernard Keavney, Maciej Tomaszewski, Nilesh J. Samani, Joanna M. M. Howson, Martin D. Tobin, Patricia B. Munroe, Georg B. Ehret, Louise V. Wain, Alan J. Gow, The International Consortium of Blood Pressure (ICBP) 1000G Analyses, The CHD Exome+ Consortium, The ExomeBP Consortium, The T2D-GENES Consortium, The GoT2DGenes Consortium, The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium, The International Genomics of Blood Pressure (iGEN -BP) Consortium, for The UK Biobank CardioMetabolic Consortium BP working group Louise

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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 - 1 Mar 2017

ASJC Scopus subject areas

Genetics

UN SDGs

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

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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., Segura Lepe, M. P., O'Reilly, P. F., Knight, J., ... for The UK Biobank CardioMetabolic Consortium BP working group Louise (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.",

author = "Warren, {Helen R.} and Evangelos Evangelou and Cabrera, {Claudia P.} and He Gao and Meixia Ren and Borbala Mifsud and Ioanna Ntalla and Praveen Surendran and Chunyu Liu and Cook, {James P.} and Kraja, {Aldi T.} and Fotios Drenos and Marie Loh and Niek Verweij and Jonathan Marten and Ibrahim Karaman and {Segura Lepe}, {Marcelo P.} and O'Reilly, {Paul F.} and Joanne Knight and Harold Snieder and Norihiro Kato and Jiang He and {Shyong Tai}, E. and {Abdullah Said}, M. and David Porteous and Maris Alver and Neil Poulter and Martin Farrall and Gansevoort, {Ron T.} and Sandosh Padmanabhan and Reedik M{\"a}gi and Alice Stanton and John Connell and Bakker, {Stephan J. L.} and Andres Metspalu and Shields, {Denis C.} and Simon Thom and Morris Brown and Peter Sever and T{\~o}nu Esko and Caroline Hayward and {van der Harst}, Pim and Danish Saleheen and Rajiv Chowdhury and Chambers, {John C.} and Chasman, {Daniel I.} and Aravinda Chakravarti and Christopher Newton-Cheh and Lindgren, {Cecilia M.} and Daniel Levy and Kooner, {Jaspal S.} and Bernard Keavney and Maciej Tomaszewski and Samani, {Nilesh J.} and Howson, {Joanna M. M.} and Tobin, {Martin D.} and Munroe, {Patricia B.} and Ehret, {Georg B.} and Wain, {Louise V.} and Gow, {Alan J.} and {The International Consortium of Blood Pressure (ICBP) 1000G Analyses} and {The CHD Exome+ Consortium} and {The ExomeBP Consortium} and {The T2D-GENES Consortium} and {The GoT2DGenes Consortium} and {The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium} and {The International Genomics of Blood Pressure (iGEN -BP) Consortium} and {for The UK Biobank CardioMetabolic Consortium BP working group Louise}",

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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, Segura Lepe, MP, O'Reilly, PF, Knight, J, Snieder, H, Kato, N, He, J, Shyong Tai, E, Abdullah Said, M, 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, Chakravarti, A, Newton-Cheh, C, Lindgren, CM, Levy, D, Kooner, JS, Keavney, B, Tomaszewski, M, Samani, NJ, Howson, JMM, Tobin, MD, Munroe, PB, Ehret, GB, Wain, LV, Gow, AJ, The International Consortium of Blood Pressure (ICBP) 1000G Analyses, The CHD Exome+ Consortium, The ExomeBP Consortium, The T2D-GENES Consortium, The GoT2DGenes Consortium, The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium, The International Genomics of Blood Pressure (iGEN -BP) Consortium & for The UK Biobank CardioMetabolic Consortium BP working group Louise 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

TY - JOUR

T1 - Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

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 - Segura Lepe, Marcelo P.

AU - O'Reilly, Paul F.

AU - Knight, Joanne

AU - Snieder, Harold

AU - Kato, Norihiro

AU - He, Jiang

AU - Shyong Tai, E.

AU - Abdullah Said, M.

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 - Chakravarti, Aravinda

AU - Newton-Cheh, Christopher

AU - Lindgren, Cecilia M.

AU - Levy, Daniel

AU - Kooner, Jaspal S.

AU - Keavney, Bernard

AU - Tomaszewski, Maciej

AU - Samani, Nilesh J.

AU - Howson, Joanna M. M.

AU - Tobin, Martin D.

AU - Munroe, Patricia B.

AU - Ehret, Georg B.

AU - Wain, Louise V.

AU - Gow, Alan J.

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

AU - The CHD Exome+ Consortium

AU - The ExomeBP Consortium

AU - The T2D-GENES Consortium

AU - The GoT2DGenes Consortium

AU - The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium

AU - The International Genomics of Blood Pressure (iGEN -BP) Consortium

AU - for The UK Biobank CardioMetabolic Consortium BP working group Louise

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

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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U2 - 10.1038/ng.3768

DO - 10.1038/ng.3768

M3 - Article

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AN - SCOPUS:85010952930

SN - 1061-4036

VL - 49

SP - 403

EP - 415

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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