Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Louise V. Wain; Germaine C. Verwoert; Paul F. O'Reilly; Gang Shi; Toby Johnson; Andrew D. Johnson; Murielle Bochud; Kenneth M. Rice; Peter Henneman; Albert V. Smith; Georg B. Ehret; Najaf Amin; Martin G. Larson; Vincent Mooser; David Hadley; Marcus Doerr; Joshua C. Bis; Thor Aspelund; Tonu Esko; A. Cecile J. W. Janssens; Jing Hua Zhao; Simon Heath; Maris Laan; Jingyuan Fu; Giorgio Pistis; Jian'an Luan; Pankaj Arora; Gavin Lucas; Nicola Pirastu; Irene Pichler; Anne U. Jackson; Rebecca J. Webster; Feng Zhang; John F. Peden; Helena Schmidt; Toshiko Tanaka; Harry Campbell; Wilmar Igl; Yuri Milaneschi; Jouke-Jan Hottenga; Veronique Vitart; Daniel I. Chasman; Stella Trompet; Jennifer L. Bragg-Gresham; Behrooz Z. Alizadeh; Ilja M. Nolte; Melanie M. van der Klauw; Ronald P. Stolk; Harold Snieder; Ko Willems van Dijk; Lifelines Cohort Study; EchoGen Consortium; AortaGen Consortium; CHARGE Consortium Heart Failure; KidneyGen Consortium; CKDGen Consortium; Cardiogenics Consortium; CARDIOGRAM

doi:10.1038/ng.922

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Louise V. Wain, Germaine C. Verwoert, Paul F. O'Reilly, Gang Shi, Toby Johnson, Andrew D. Johnson, Murielle Bochud, Kenneth M. Rice, Peter Henneman, Albert V. Smith, Georg B. Ehret, Najaf Amin, Martin G. Larson, Vincent Mooser, David Hadley, Marcus Doerr, Joshua C. Bis, Thor Aspelund, Tonu Esko, A. Cecile J. W. JanssensJing Hua Zhao, Simon Heath, Maris Laan, Jingyuan Fu, Giorgio Pistis, Jian'an Luan, Pankaj Arora, Gavin Lucas, Nicola Pirastu, Irene Pichler, Anne U. Jackson, Rebecca J. Webster, Feng Zhang, John F. Peden, Helena Schmidt, Toshiko Tanaka, Harry Campbell, Wilmar Igl, Yuri Milaneschi, Jouke-Jan Hottenga, Veronique Vitart, Daniel I. Chasman, Stella Trompet, Jennifer L. Bragg-Gresham, Behrooz Z. Alizadeh, Ilja M. Nolte, Melanie M. van der Klauw, Ronald P. Stolk, Harold Snieder, Ko Willems van Dijk, Lifelines Cohort Study, EchoGen Consortium, AortaGen Consortium, CHARGE Consortium Heart Failure, KidneyGen Consortium, CKDGen Consortium, Cardiogenics Consortium, CARDIOGRAM

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Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Original language	English
Pages (from-to)	1005-U122
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.922
Publication status	Published - Oct-2011

Keywords

ADRENERGIC-RECEPTOR TRAFFICKING
CARDIOVASCULAR-DISEASE RISK
BLOOD-PRESSURE
HEART-FAILURE
HYPERTENSION
METAANALYSIS
MORTALITY
GENE
MICE
RELEVANCE

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Wain, L. V., Verwoert, G. C., O'Reilly, P. F., Shi, G., Johnson, T., Johnson, A. D., Bochud, M., Rice, K. M., Henneman, P., Smith, A. V., Ehret, G. B., Amin, N., Larson, M. G., Mooser, V., Hadley, D., Doerr, M., Bis, J. C., Aspelund, T., Esko, T., ... CARDIOGRAM (2011). Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nature Genetics, 43(10), 1005-U122. https://doi.org/10.1038/ng.922

@article{2f90585dbd8848a793b4fee317d8d9a6,

title = "Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure",

abstract = "Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.",

keywords = "ADRENERGIC-RECEPTOR TRAFFICKING, CARDIOVASCULAR-DISEASE RISK, BLOOD-PRESSURE, HEART-FAILURE, HYPERTENSION, METAANALYSIS, MORTALITY, GENE, MICE, RELEVANCE",

author = "Wain, {Louise V.} and Verwoert, {Germaine C.} and O'Reilly, {Paul F.} and Gang Shi and Toby Johnson and Johnson, {Andrew D.} and Murielle Bochud and Rice, {Kenneth M.} and Peter Henneman and Smith, {Albert V.} and Ehret, {Georg B.} and Najaf Amin and Larson, {Martin G.} and Vincent Mooser and David Hadley and Marcus Doerr and Bis, {Joshua C.} and Thor Aspelund and Tonu Esko and Janssens, {A. Cecile J. W.} and Zhao, {Jing Hua} and Simon Heath and Maris Laan and Jingyuan Fu and Giorgio Pistis and Jian'an Luan and Pankaj Arora and Gavin Lucas and Nicola Pirastu and Irene Pichler and Jackson, {Anne U.} and Webster, {Rebecca J.} and Feng Zhang and Peden, {John F.} and Helena Schmidt and Toshiko Tanaka and Harry Campbell and Wilmar Igl and Yuri Milaneschi and Jouke-Jan Hottenga and Veronique Vitart and Chasman, {Daniel I.} and Stella Trompet and Bragg-Gresham, {Jennifer L.} and Alizadeh, {Behrooz Z.} and Nolte, {Ilja M.} and {van der Klauw}, {Melanie M.} and Stolk, {Ronald P.} and Harold Snieder and {van Dijk}, {Ko Willems} and {Lifelines Cohort Study} and {EchoGen Consortium} and {AortaGen Consortium} and {CHARGE Consortium Heart Failure} and {KidneyGen Consortium} and {CKDGen Consortium} and {Cardiogenics Consortium} and CARDIOGRAM",

year = "2011",

month = oct,

doi = "10.1038/ng.922",

language = "English",

volume = "43",

pages = "1005--U122",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Doerr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, ACJW, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, J-J, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ , Nolte, IM , van der Klauw, MM , Stolk, RP , Snieder, H, van Dijk, KW, Lifelines Cohort Study, EchoGen Consortium, AortaGen Consortium, CHARGE Consortium Heart Failure, KidneyGen Consortium, CKDGen Consortium, Cardiogenics Consortium & CARDIOGRAM 2011, 'Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure', Nature Genetics, vol. 43, no. 10, pp. 1005-U122. https://doi.org/10.1038/ng.922

TY - JOUR

T1 - Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

AU - Wain, Louise V.

AU - Verwoert, Germaine C.

AU - O'Reilly, Paul F.

AU - Shi, Gang

AU - Johnson, Toby

AU - Johnson, Andrew D.

AU - Bochud, Murielle

AU - Rice, Kenneth M.

AU - Henneman, Peter

AU - Smith, Albert V.

AU - Ehret, Georg B.

AU - Amin, Najaf

AU - Larson, Martin G.

AU - Mooser, Vincent

AU - Hadley, David

AU - Doerr, Marcus

AU - Bis, Joshua C.

AU - Aspelund, Thor

AU - Esko, Tonu

AU - Janssens, A. Cecile J. W.

AU - Zhao, Jing Hua

AU - Heath, Simon

AU - Laan, Maris

AU - Fu, Jingyuan

AU - Pistis, Giorgio

AU - Luan, Jian'an

AU - Arora, Pankaj

AU - Lucas, Gavin

AU - Pirastu, Nicola

AU - Pichler, Irene

AU - Jackson, Anne U.

AU - Webster, Rebecca J.

AU - Zhang, Feng

AU - Peden, John F.

AU - Schmidt, Helena

AU - Tanaka, Toshiko

AU - Campbell, Harry

AU - Igl, Wilmar

AU - Milaneschi, Yuri

AU - Hottenga, Jouke-Jan

AU - Vitart, Veronique

AU - Chasman, Daniel I.

AU - Trompet, Stella

AU - Bragg-Gresham, Jennifer L.

AU - Alizadeh, Behrooz Z.

AU - Nolte, Ilja M.

AU - van der Klauw, Melanie M.

AU - Stolk, Ronald P.

AU - Snieder, Harold

AU - van Dijk, Ko Willems

AU - Lifelines Cohort Study

AU - EchoGen Consortium

AU - AortaGen Consortium

AU - CHARGE Consortium Heart Failure

AU - KidneyGen Consortium

AU - CKDGen Consortium

AU - Cardiogenics Consortium

AU - CARDIOGRAM

PY - 2011/10

Y1 - 2011/10

N2 - Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

AB - Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

KW - ADRENERGIC-RECEPTOR TRAFFICKING

KW - CARDIOVASCULAR-DISEASE RISK

KW - BLOOD-PRESSURE

KW - HEART-FAILURE

KW - HYPERTENSION

KW - METAANALYSIS

KW - MORTALITY

KW - GENE

KW - MICE

KW - RELEVANCE

U2 - 10.1038/ng.922

DO - 10.1038/ng.922

M3 - Letter

C2 - 21909110

SN - 1061-4036

VL - 43

SP - 1005-U122

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Abstract

Keywords

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