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

Int Consortium Blood Pressure ICBP; CHD Exome Consortium; ExomeBP Consortium; T2D-GENES Consortium; GoT2D Genes Consortium; CHARGE BP Exome Consortium; iGEN-BP Consortium; UK Biobank CardioMetab Consortium; BIOS Consortium; Lifelines Cohort Study; Understanding Soc Sci Grp; 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 Magi; Caroline Hayward; Peter K. Joshi; Lorna M. Lopez; Jonathan Marten; Sarah E. Harris; Archie Campbell; Harry Campbell; Gail Davies; Alan J. Gow; David C. M. Liewald; Andrew D. Morris; Alison Pattie; Igor Rudan; Alan F. Wright; John M. Starr; Caroline Hayward; Veronique Vitart; Ian J. Deary; James F. Wilson

doi:10.1038/ng.3768

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

Int Consortium Blood Pressure ICBP, CHD Exome Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2D Genes Consortium, CHARGE BP Exome Consortium, iGEN-BP Consortium, UK Biobank CardioMetab Consortium, BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Helen R. Warren, Evangelos Evangelou, Claudia P. Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu LiuJames 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 Magi, Caroline Hayward, Peter K. Joshi, Lorna M. Lopez, Jonathan Marten, Sarah E. Harris, Archie Campbell, Harry Campbell, Gail Davies, Alan J. Gow, David C. M. Liewald, Andrew D. Morris, Alison Pattie, Igor Rudan, Alan F. Wright, John M. Starr, Caroline Hayward, Veronique Vitart, Ian J. Deary, James F. Wilson

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

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

Keywords / Materials (for Non-textual outputs)

CORONARY-ARTERY-DISEASE
ENDOTHELIAL-CELL
MYOCARDIAL-INFARCTION
NEUROTROPHIC FACTOR
NADPH OXIDASE
UK BIOBANK
KEY ROLE
IN-VIVO
HYPERTENSION
COMMON

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Int Consortium Blood Pressure ICBP, CHD Exome Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2D Genes Consortium, CHARGE BP Exome Consortium, iGEN-BP Consortium, UK Biobank CardioMetab Consortium, BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Warren, H. R., Evangelou, E., Cabrera, C. P., Gao, H., Ren, M., Mifsud, B., Ntalla, I., Surendran, P., ... Wilson, J. F. (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

@article{03cab8023564451fa67d46d46d007aff,

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

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.",

keywords = "CORONARY-ARTERY-DISEASE, ENDOTHELIAL-CELL, MYOCARDIAL-INFARCTION, NEUROTROPHIC FACTOR, NADPH OXIDASE, UK BIOBANK, KEY ROLE, IN-VIVO, HYPERTENSION, COMMON",

author = "{Int Consortium Blood Pressure ICBP} and {CHD Exome Consortium} and {ExomeBP Consortium} and {T2D-GENES Consortium} and {GoT2D Genes Consortium} and {CHARGE BP Exome Consortium} and {iGEN-BP Consortium} and {UK Biobank CardioMetab Consortium} and {BIOS Consortium} and {Lifelines Cohort Study} and {Understanding Soc Sci Grp} and 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 Lepe, {Marcelo P. Segura} and O'Reilly, {Paul F.} and Joanne Knight and Harold Snieder and Norihiro Kato and Jiang He and Tai, {E. Shyong} and Said, {M. Abdullah} and David Porteous and Maris Alver and Neil Poulter and Martin Farrall and Gansevoort, {Ron T.} and Sandosh Padmanabhan and Reedik Magi and Caroline Hayward and Joshi, {Peter K.} and Lopez, {Lorna M.} and Jonathan Marten and Harris, {Sarah E.} and Archie Campbell and Harry Campbell and Gail Davies and Gow, {Alan J.} and Liewald, {David C. M.} and Morris, {Andrew D.} and Alison Pattie and Igor Rudan and Wright, {Alan F.} and Starr, {John M.} and Caroline Hayward and Veronique Vitart and Deary, {Ian J.} and Wilson, {James F.}",

year = "2017",

month = mar,

doi = "10.1038/ng.3768",

language = "English",

volume = "49",

pages = "403--415",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

Int Consortium Blood Pressure ICBP, CHD Exome Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2D Genes Consortium, CHARGE BP Exome Consortium, iGEN-BP Consortium, UK Biobank CardioMetab Consortium, BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, 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, Magi, R, Hayward, C, Joshi, PK, Lopez, LM, Marten, J, Harris, SE , Campbell, A , Campbell, H , Davies, G, Gow, AJ, Liewald, DCM, Morris, AD, Pattie, A, Rudan, I, Wright, AF, Starr, JM, Hayward, C , Vitart, V , Deary, IJ & Wilson, JF 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 - Int Consortium Blood Pressure ICBP

AU - CHD Exome Consortium

AU - ExomeBP Consortium

AU - T2D-GENES Consortium

AU - GoT2D Genes Consortium

AU - CHARGE BP Exome Consortium

AU - iGEN-BP Consortium

AU - UK Biobank CardioMetab Consortium

AU - BIOS Consortium

AU - Lifelines Cohort Study

AU - Understanding Soc Sci Grp

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 - Magi, Reedik

AU - Hayward, Caroline

AU - Joshi, Peter K.

AU - Lopez, Lorna M.

AU - Marten, Jonathan

AU - Harris, Sarah E.

AU - Campbell, Archie

AU - Campbell, Harry

AU - Davies, Gail

AU - Gow, Alan J.

AU - Liewald, David C. M.

AU - Morris, Andrew D.

AU - Pattie, Alison

AU - Rudan, Igor

AU - Wright, Alan F.

AU - Starr, John M.

AU - Hayward, Caroline

AU - Vitart, Veronique

AU - Deary, Ian J.

AU - Wilson, James F.

PY - 2017/3

Y1 - 2017/3

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.

KW - CORONARY-ARTERY-DISEASE

KW - ENDOTHELIAL-CELL

KW - MYOCARDIAL-INFARCTION

KW - NEUROTROPHIC FACTOR

KW - NADPH OXIDASE

KW - UK BIOBANK

KW - KEY ROLE

KW - IN-VIVO

KW - HYPERTENSION

KW - COMMON

U2 - 10.1038/ng.3768

DO - 10.1038/ng.3768

M3 - Article

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

Keywords / Materials (for Non-textual outputs)

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