Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Georg B. Ehret; Patricia B. Munroe; Kenneth M. Rice; Murielle Bochud; Andrew D. Johnson; Daniel I. Chasman; Albert V. Smith; Martin D. Tobin; Germaine C. Verwoert; Shih-Jen Hwang; Vasyl Pihur; Peter Vollenweider; Paul F. O'Reilly; Najaf Amin; Jennifer L. Bragg-Gresham; Alexander Teumer; Nicole L. Glazer; Lenore Launer; Jing Hua Zhao; Yurii Aulchenko; Simon Heath; Siim Sober; Afshin Parsa; Jian'an Luan; Pankaj Arora; Abbas Dehghan; Feng Zhang; Gavin Lucas; Andrew A. Hicks; Anne U. Jackson; John F. Peden; Toshiko Tanaka; Sarah H. Wild; Igor Rudan; Wilmar Igl; Yuri Milaneschi; Alex N. Parker; Cristiano Fava; John C. Chambers; Ervin R. Fox; Meena Kumari; Min Jin Go; Pim van der Harst; Wen Hong Linda Kao; Marketa Sjogren; D. G. Vinay; Myriam Alexander; Yasuharu Tabara; Sue Shaw-Hawkins; John M. Connell; CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium

doi:10.1038/nature10405

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Andrew D. Johnson, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O'Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii AulchenkoSimon Heath, Siim Sober, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N. Parker, Cristiano Fava, John C. Chambers, Ervin R. Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjogren, D. G. Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, John M. Connell, CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium

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

1695 Citations (Scopus)

Abstract

Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Original language	English
Pages (from-to)	103-109
Number of pages	7
Journal	Nature
Volume	478
Issue number	7367
DOIs	https://doi.org/10.1038/nature10405
Publication status	Published - 6 Oct 2011

Keywords

GENOME-WIDE ASSOCIATION
COMMON VARIANTS
HYPERTENSION
METAANALYSIS
LOCI
POPULATION
RELEVANCE
RECEPTOR
CLONING
HEALTH

UN SDGs

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

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10.1038/nature10405

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Ehret, G. B., Munroe, P. B., Rice, K. M., Bochud, M., Johnson, A. D., Chasman, D. I., Smith, A. V., Tobin, M. D., Verwoert, G. C., Hwang, S.-J., Pihur, V., Vollenweider, P., O'Reilly, P. F., Amin, N., Bragg-Gresham, J. L., Teumer, A., Glazer, N. L., Launer, L., Zhao, J. H., ... CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478(7367), 103-109. https://doi.org/10.1038/nature10405

@article{3b2377c47ebe4c2387aa8f667ed4455b,

title = "Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk",

abstract = "Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.",

keywords = "GENOME-WIDE ASSOCIATION, COMMON VARIANTS, HYPERTENSION, METAANALYSIS, LOCI, POPULATION, RELEVANCE, RECEPTOR, CLONING, HEALTH",

author = "Ehret, {Georg B.} and Munroe, {Patricia B.} and Rice, {Kenneth M.} and Murielle Bochud and Johnson, {Andrew D.} and Chasman, {Daniel I.} and Smith, {Albert V.} and Tobin, {Martin D.} and Verwoert, {Germaine C.} and Shih-Jen Hwang and Vasyl Pihur and Peter Vollenweider and O'Reilly, {Paul F.} and Najaf Amin and Bragg-Gresham, {Jennifer L.} and Alexander Teumer and Glazer, {Nicole L.} and Lenore Launer and Zhao, {Jing Hua} and Yurii Aulchenko and Simon Heath and Siim Sober and Afshin Parsa and Jian'an Luan and Pankaj Arora and Abbas Dehghan and Feng Zhang and Gavin Lucas and Hicks, {Andrew A.} and Jackson, {Anne U.} and Peden, {John F.} and Toshiko Tanaka and Wild, {Sarah H.} and Igor Rudan and Wilmar Igl and Yuri Milaneschi and Parker, {Alex N.} and Cristiano Fava and Chambers, {John C.} and Fox, {Ervin R.} and Meena Kumari and Go, {Min Jin} and {van der Harst}, Pim and Kao, {Wen Hong Linda} and Marketa Sjogren and Vinay, {D. G.} and Myriam Alexander and Yasuharu Tabara and Sue Shaw-Hawkins and Connell, {John M.} and {CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium}",

year = "2011",

month = oct,

day = "6",

doi = "10.1038/nature10405",

language = "English",

volume = "478",

pages = "103--109",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7367",

}

Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, J, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Connell, JM & CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium 2011, 'Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk', Nature, vol. 478, no. 7367, pp. 103-109. https://doi.org/10.1038/nature10405

TY - JOUR

T1 - Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

AU - Ehret, Georg B.

AU - Munroe, Patricia B.

AU - Rice, Kenneth M.

AU - Bochud, Murielle

AU - Johnson, Andrew D.

AU - Chasman, Daniel I.

AU - Smith, Albert V.

AU - Tobin, Martin D.

AU - Verwoert, Germaine C.

AU - Hwang, Shih-Jen

AU - Pihur, Vasyl

AU - Vollenweider, Peter

AU - O'Reilly, Paul F.

AU - Amin, Najaf

AU - Bragg-Gresham, Jennifer L.

AU - Teumer, Alexander

AU - Glazer, Nicole L.

AU - Launer, Lenore

AU - Zhao, Jing Hua

AU - Aulchenko, Yurii

AU - Heath, Simon

AU - Sober, Siim

AU - Parsa, Afshin

AU - Luan, Jian'an

AU - Arora, Pankaj

AU - Dehghan, Abbas

AU - Zhang, Feng

AU - Lucas, Gavin

AU - Hicks, Andrew A.

AU - Jackson, Anne U.

AU - Peden, John F.

AU - Tanaka, Toshiko

AU - Wild, Sarah H.

AU - Rudan, Igor

AU - Igl, Wilmar

AU - Milaneschi, Yuri

AU - Parker, Alex N.

AU - Fava, Cristiano

AU - Chambers, John C.

AU - Fox, Ervin R.

AU - Kumari, Meena

AU - Go, Min Jin

AU - van der Harst, Pim

AU - Kao, Wen Hong Linda

AU - Sjogren, Marketa

AU - Vinay, D. G.

AU - Alexander, Myriam

AU - Tabara, Yasuharu

AU - Shaw-Hawkins, Sue

AU - Connell, John M.

AU - CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium

PY - 2011/10/6

Y1 - 2011/10/6

N2 - Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

AB - Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

KW - GENOME-WIDE ASSOCIATION

KW - COMMON VARIANTS

KW - HYPERTENSION

KW - METAANALYSIS

KW - LOCI

KW - POPULATION

KW - RELEVANCE

KW - RECEPTOR

KW - CLONING

KW - HEALTH

U2 - 10.1038/nature10405

DO - 10.1038/nature10405

M3 - Article

C2 - 21909115

SN - 0028-0836

VL - 478

SP - 103

EP - 109

JO - Nature

JF - Nature

IS - 7367

ER -

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Abstract

Keywords

UN SDGs

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