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 Dörr; Joshua C Bis; Thor Aspelund; Tõnu 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; John C Chambers; Xiuqing Guo; Terho Lehtimäki; Wendy L McArdle; Lyle J Palmer; LifeLines Cohort Study

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 Dörr, Joshua C Bis, Thor Aspelund, Tõnu 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, John C Chambers, Xiuqing Guo, Terho Lehtimäki, Wendy L McArdle, Lyle J Palmer, LifeLines Cohort Study

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

301 Citations (Scopus)

Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. 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 × 10(-8) to P = 2.3 × 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)	1005-11
Number of pages	7
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.922
Publication status	Published - 2011

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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., Dörr, M., Bis, J. C., Aspelund, T., Esko, T., ... LifeLines Cohort Study (2011). Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nature Genetics, 43(10), 1005-11. https://doi.org/10.1038/ng.922

Wain, Louise V ; Verwoert, Germaine C ; O'Reilly, Paul F ; Shi, Gang ; Johnson, Toby ; Johnson, Andrew D ; Bochud, Murielle ; Rice, Kenneth M ; Henneman, Peter ; Smith, Albert V ; Ehret, Georg B ; Amin, Najaf ; Larson, Martin G ; Mooser, Vincent ; Hadley, David ; Dörr, Marcus ; Bis, Joshua C ; Aspelund, Thor ; Esko, Tõnu ; Janssens, A Cecile J W ; Zhao, Jing Hua ; Heath, Simon ; Laan, Maris ; Fu, Jingyuan ; Pistis, Giorgio ; Luan, Jian'an ; Arora, Pankaj ; Lucas, Gavin ; Pirastu, Nicola ; Pichler, Irene ; Jackson, Anne U ; Webster, Rebecca J ; Zhang, Feng ; Peden, John F ; Schmidt, Helena ; Tanaka, Toshiko ; Campbell, Harry ; Igl, Wilmar ; Milaneschi, Yuri ; Hottenga, Jouke-Jan ; Vitart, Veronique ; Chasman, Daniel I ; Trompet, Stella ; Bragg-Gresham, Jennifer L ; Alizadeh, Behrooz Z ; Chambers, John C ; Guo, Xiuqing ; Lehtimäki, Terho ; McArdle, Wendy L ; Palmer, Lyle J ; LifeLines Cohort Study. / Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. In: Nature Genetics. 2011 ; Vol. 43, No. 10. pp. 1005-11.

@article{7190f09ae4bc4efeaf54f0e18b0f855b,

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. 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 × 10(-8) to P = 2.3 × 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.",

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 D{\"o}rr and Bis, {Joshua C} and Thor Aspelund and T{\~o}nu 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 Chambers, {John C} and Xiuqing Guo and Terho Lehtim{\"a}ki and McArdle, {Wendy L} and Palmer, {Lyle J} and {LifeLines Cohort Study}",

year = "2011",

doi = "10.1038/ng.922",

language = "English",

volume = "43",

pages = "1005--11",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

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, Dörr, 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, Chambers, JC, Guo, X, Lehtimäki, T, McArdle, WL, Palmer, LJ & LifeLines Cohort Study 2011, 'Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure', Nature Genetics, vol. 43, no. 10, pp. 1005-11. https://doi.org/10.1038/ng.922

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. / Wain, Louise V; Verwoert, Germaine C; O'Reilly, Paul F; Shi, Gang; Johnson, Toby; Johnson, Andrew D; Bochud, Murielle; Rice, Kenneth M; Henneman, Peter; Smith, Albert V; Ehret, Georg B; Amin, Najaf; Larson, Martin G; Mooser, Vincent; Hadley, David; Dörr, Marcus; Bis, Joshua C; Aspelund, Thor; Esko, Tõnu; Janssens, A Cecile J W; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U; Webster, Rebecca J; Zhang, Feng; Peden, John F; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I; Trompet, Stella; Bragg-Gresham, Jennifer L; Alizadeh, Behrooz Z; Chambers, John C; Guo, Xiuqing; Lehtimäki, Terho; McArdle, Wendy L; Palmer, Lyle J; LifeLines Cohort Study.

In: Nature Genetics, Vol. 43, No. 10, 2011, p. 1005-11.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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 - Dörr, Marcus

AU - Bis, Joshua C

AU - Aspelund, Thor

AU - Esko, Tõnu

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 - Chambers, John C

AU - Guo, Xiuqing

AU - Lehtimäki, Terho

AU - McArdle, Wendy L

AU - Palmer, Lyle J

AU - LifeLines Cohort Study

PY - 2011

Y1 - 2011

N2 - Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. 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 × 10(-8) to P = 2.3 × 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. 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 × 10(-8) to P = 2.3 × 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.

U2 - 10.1038/ng.922

DO - 10.1038/ng.922

M3 - Article (Academic Journal)

C2 - 21909110

VL - 43

SP - 1005

EP - 1011

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -