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

LV Wain; Germaine Verwoert; PF O'Reilly; G Shi; T Johnson; AD Johnson; M Bochud; KM Rice; Peter Henneman; AV Smith; GB Ehret; Najaf Amin; MG Larson; V Mooser; D Hadley; M Dorr; JC Bis; T Aspelund; T Esko; Cecile Janssens; JH Zhao; S Heath; M Laan; JY Fu; G Pistis; JA Luan; M Arora; G Lucas; N Pirastu; I Pichler; AU Jackson; RJ Webster; F Zhang; JF Peden; Heléna Schmidt; T Tanaka; H Campbell; W Igl; Y Milaneschi; JJ (Jouke Jan) Hottenga; V Vitart; DI Chasman; S Trompet; JL Bragg-Gresham; BZ Alizadeh; JC Chambers; XQ Guo; T Lehtimaki; B Kuhnel; LM Lopez; O Polasek; M Boban; CP Nelson; AC Morrison; V Pihur; SK Ganesh; Bert Hofman; Suman Kundu; F.U.S. Mattace Raso; Fernando Rivadeneira; E.J.G. Sijbrands; André Uitterlinden; SJ Hwang; RS Vasan; TJ Wang; S Bergmann; P Vollenweider; G Waeber; J Laitinen; A Pouta; P Zitting; WL McArdle; HK Kroemer; U Volker; H Volzke; NL Glazer; KD Taylor; TB Harris; H Alavere; T Haller; A Keis; ML Tammesoo; Yuriy Aulchenko; I Barroso; KT Khaw; P Galan; S Hercberg; M Lathrop; S Eyheramendy; E Org; S Sober; XW Lu; IM (Ilja) Nolte; BW Penninx; T Corre; C Masciullo; C Sala; L Groop; BF Voight; O Melander; CJ O'Donnell; V Salomaa; AP d'Adamo; A Fabretto; F Faletra; S Ulivi; MF Del Greco; M Facheris; FS Collins; RN Bergman; JP Beilby; J Hung; AW Musk; M Mangino; SY Shin; N Soranzo; H Watkins; A Goel; A Hamsten; P Gider; M Loitfelder; M Zeginigg; D Hernandez; SS Najjar; P Navarro; SH Wild; AM Corsi; A Singleton; EJC de Geus; G Willemsen; AN Parker; LM Rose; B Buckley; D Stott; M Orru; M Uda; MM (Melanie) van der Klauw; WH Zhang; XZ Li; J Scott; YDI Chen; GL Burke; M Kahonen; J Viikari; A Doring; T Meitinger; G Davies; JM Starr; V Emilsson; A Plump; JH Lindeman; PAC 't Hoen; IR Konig; Janine Felix; R Clarke; JC Hopewell; H Ongen; Monique Breteler; S Debette; AL DeStefano; M Fornage; GF Mitchell; NL Smith; H Holm; K Stefansson; G Thorleifsson; U Thorsteinsdottir; NJ Samani; M Preuss; I Rudan; C Hayward; IJ Deary; HE Wichmann; OT Raitakari; W Palmas; JS Kooner; RP (Ronald) Stolk; JW Jukema; AF Wright; DI Boomsma; S Bandinelli; UB Gyllensten; JF Wilson; L Ferrucci; R Schmidt; M Farrall; TD Spector; LJ Palmer; J Tuomilehto; A Pfeufer; P Gasparini; D Siscovick; D Altshuler; RJF Loos; D Toniolo; H Snieder; C Gieger; P Meneton; NJ Wareham; Ben Oostra; A Metspalu; L Launer; R Rettig; DP Strachan; JS Beckmann; JCM Witteman; J Erdmann; KW van Dijk; E Boerwinkle; M Boehnke; PM Ridker; MR Jarvelin; A Chakravarti; GR Abecasis; V Gudnason; C Newton-Cheh; D Levy; PB Munroe; BM Psaty; MJ Caulfield; DC Rao; MD Tobin; P Elliott; Cornelia Duijn

doi:10.1038/ng.922

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

LV Wain, Germaine Verwoert, PF O'Reilly, G Shi, T Johnson, AD Johnson, M Bochud, KM Rice, Peter Henneman, AV Smith, GB Ehret, Najaf Amin, MG Larson, V Mooser, D Hadley, M Dorr, JC Bis, T Aspelund, T Esko, Cecile JanssensJH Zhao, S Heath, M Laan, JY Fu, G Pistis, JA Luan, M Arora, G Lucas, N Pirastu, I Pichler, AU Jackson, RJ Webster, F Zhang, JF Peden, Heléna Schmidt, T Tanaka, H Campbell, W Igl, Y Milaneschi, JJ (Jouke Jan) Hottenga, V Vitart, DI Chasman, S Trompet, JL Bragg-Gresham, BZ Alizadeh, JC Chambers, XQ Guo, T Lehtimaki, B Kuhnel, LM Lopez, O Polasek, M Boban, CP Nelson, AC Morrison, V Pihur, SK Ganesh, Bert Hofman, Suman Kundu, F.U.S. Mattace Raso, Fernando Rivadeneira, E.J.G. Sijbrands, André Uitterlinden, SJ Hwang, RS Vasan, TJ Wang, S Bergmann, P Vollenweider, G Waeber, J Laitinen, A Pouta, P Zitting, WL McArdle, HK Kroemer, U Volker, H Volzke, NL Glazer, KD Taylor, TB Harris, H Alavere, T Haller, A Keis, ML Tammesoo, Yuriy Aulchenko, I Barroso, KT Khaw, P Galan, S Hercberg, M Lathrop, S Eyheramendy, E Org, S Sober, XW Lu, IM (Ilja) Nolte, BW Penninx, T Corre, C Masciullo, C Sala, L Groop, BF Voight, O Melander, CJ O'Donnell, V Salomaa, AP d'Adamo, A Fabretto, F Faletra, S Ulivi, MF Del Greco, M Facheris, FS Collins, RN Bergman, JP Beilby, J Hung, AW Musk, M Mangino, SY Shin, N Soranzo, H Watkins, A Goel, A Hamsten, P Gider, M Loitfelder, M Zeginigg, D Hernandez, SS Najjar, P Navarro, SH Wild, AM Corsi, A Singleton, EJC de Geus, G Willemsen, AN Parker, LM Rose, B Buckley, D Stott, M Orru, M Uda, MM (Melanie) van der Klauw, WH Zhang, XZ Li, J Scott, YDI Chen, GL Burke, M Kahonen, J Viikari, A Doring, T Meitinger, G Davies, JM Starr, V Emilsson, A Plump, JH Lindeman, PAC 't Hoen, IR Konig, Janine Felix, R Clarke, JC Hopewell, H Ongen, Monique Breteler, S Debette, AL DeStefano, M Fornage, GF Mitchell, NL Smith, H Holm, K Stefansson, G Thorleifsson, U Thorsteinsdottir, NJ Samani, M Preuss, I Rudan, C Hayward, IJ Deary, HE Wichmann, OT Raitakari, W Palmas, JS Kooner, RP (Ronald) Stolk, JW Jukema, AF Wright, DI Boomsma, S Bandinelli, UB Gyllensten, JF Wilson, L Ferrucci, R Schmidt, M Farrall, TD Spector, LJ Palmer, J Tuomilehto, A Pfeufer, P Gasparini, D Siscovick, D Altshuler, RJF Loos, D Toniolo, H Snieder, C Gieger, P Meneton, NJ Wareham, Ben Oostra, A Metspalu, L Launer, R Rettig, DP Strachan, JS Beckmann, JCM Witteman, J Erdmann, KW van Dijk, E Boerwinkle, M Boehnke, PM Ridker, MR Jarvelin, A Chakravarti, GR Abecasis, V Gudnason, C Newton-Cheh, D Levy, PB Munroe, BM Psaty, MJ Caulfield, DC Rao, MD Tobin, P Elliott, Cornelia Duijn

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

365 Citations (Scopus)

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	Undefined/Unknown
Pages (from-to)	1005-U122
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.922
Publication status	Published - 2011

Research programs

EMC COEUR-09
EMC MGC-02-96-01
EMC MM-01-25-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC NIHES-01-64-03
EMC OR-01-39-08

Access to Document

10.1038/ng.922

http://hdl.handle.net/1765/30820

Cite this

Wain, LV., Verwoert, G., 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., Dorr, M., Bis, JC., Aspelund, T., Esko, T., ... Duijn, C. (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{d5998220eca5495dad651f76d757ab64,

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.",

author = "LV Wain and Germaine Verwoert and PF O'Reilly and G Shi and T Johnson and AD Johnson and M Bochud and KM Rice and Peter Henneman and AV Smith and GB Ehret and Najaf Amin and MG Larson and V Mooser and D Hadley and M Dorr and JC Bis and T Aspelund and T Esko and Cecile Janssens and JH Zhao and S Heath and M Laan and JY Fu and G Pistis and JA Luan and M Arora and G Lucas and N Pirastu and I Pichler and AU Jackson and RJ Webster and F Zhang and JF Peden and Hel{\'e}na Schmidt and T Tanaka and H Campbell and W Igl and Y Milaneschi and Hottenga, {JJ (Jouke Jan)} and V Vitart and DI Chasman and S Trompet and JL Bragg-Gresham and BZ Alizadeh and JC Chambers and XQ Guo and T Lehtimaki and B Kuhnel and LM Lopez and O Polasek and M Boban and CP Nelson and AC Morrison and V Pihur and SK Ganesh and Bert Hofman and Suman Kundu and {Mattace Raso}, F.U.S. and Fernando Rivadeneira and E.J.G. Sijbrands and Andr{\'e} Uitterlinden and SJ Hwang and RS Vasan and TJ Wang and S Bergmann and P Vollenweider and G Waeber and J Laitinen and A Pouta and P Zitting and WL McArdle and HK Kroemer and U Volker and H Volzke and NL Glazer and KD Taylor and TB Harris and H Alavere and T Haller and A Keis and ML Tammesoo and Yuriy Aulchenko and I Barroso and KT Khaw and P Galan and S Hercberg and M Lathrop and S Eyheramendy and E Org and S Sober and XW Lu and Nolte, {IM (Ilja)} and BW Penninx and T Corre and C Masciullo and C Sala and L Groop and BF Voight and O Melander and CJ O'Donnell and V Salomaa and AP d'Adamo and A Fabretto and F Faletra and S Ulivi and {Del Greco}, MF and M Facheris and FS Collins and RN Bergman and JP Beilby and J Hung and AW Musk and M Mangino and SY Shin and N Soranzo and H Watkins and A Goel and A Hamsten and P Gider and M Loitfelder and M Zeginigg and D Hernandez and SS Najjar and P Navarro and SH Wild and AM Corsi and A Singleton and {de Geus}, EJC and G Willemsen and AN Parker and LM Rose and B Buckley and D Stott and M Orru and M Uda and {van der Klauw}, {MM (Melanie)} and WH Zhang and XZ Li and J Scott and YDI Chen and GL Burke and M Kahonen and J Viikari and A Doring and T Meitinger and G Davies and JM Starr and V Emilsson and A Plump and JH Lindeman and {'t Hoen}, PAC and IR Konig and Janine Felix and R Clarke and JC Hopewell and H Ongen and Monique Breteler and S Debette and AL DeStefano and M Fornage and GF Mitchell and NL Smith and H Holm and K Stefansson and G Thorleifsson and U Thorsteinsdottir and NJ Samani and M Preuss and I Rudan and C Hayward and IJ Deary and HE Wichmann and OT Raitakari and W Palmas and JS Kooner and Stolk, {RP (Ronald)} and JW Jukema and AF Wright and DI Boomsma and S Bandinelli and UB Gyllensten and JF Wilson and L Ferrucci and R Schmidt and M Farrall and TD Spector and LJ Palmer and J Tuomilehto and A Pfeufer and P Gasparini and D Siscovick and D Altshuler and RJF Loos and D Toniolo and H Snieder and C Gieger and P Meneton and NJ Wareham and Ben Oostra and A Metspalu and L Launer and R Rettig and DP Strachan and JS Beckmann and JCM Witteman and J Erdmann and {van Dijk}, KW and E Boerwinkle and M Boehnke and PM Ridker and MR Jarvelin and A Chakravarti and GR Abecasis and V Gudnason and C Newton-Cheh and D Levy and PB Munroe and BM Psaty and MJ Caulfield and DC Rao and MD Tobin and P Elliott and Cornelia Duijn",

year = "2011",

doi = "10.1038/ng.922",

language = "Undefined/Unknown",

volume = "43",

pages = "1005--U122",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Wain, LV, Verwoert, G, 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, Dorr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, C, Zhao, JH, Heath, S, Laan, M, Fu, JY, Pistis, G, Luan, JA, Arora, M, 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, JJ, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, XQ, Lehtimaki, T, Kuhnel, B, Lopez, LM, Polasek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, B, Kundu, S, Mattace Raso, FUS , Rivadeneira, F , Sijbrands, EJG , Uitterlinden, A, Hwang, SJ, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Volker, U, Volzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, ML, Aulchenko, Y, Barroso, I, Khaw, KT, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sober, S, Lu, XW, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco, MF, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, SY, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJC, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, van der Klauw, MM, Zhang, WH, Li, XZ, Scott, J, Chen, YDI, Burke, GL, Kahonen, M, Viikari, J, Doring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, 't Hoen, PAC, Konig, IR, Felix, J, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, DeStefano, AL, Fornage, M, Mitchell, GF, Smith, NL, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, HE, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJF, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, B, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JCM, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, MR, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P & Duijn, C 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, LV

AU - Verwoert, Germaine

AU - O'Reilly, PF

AU - Shi, G

AU - Johnson, T

AU - Johnson, AD

AU - Bochud, M

AU - Rice, KM

AU - Henneman, Peter

AU - Smith, AV

AU - Ehret, GB

AU - Amin, Najaf

AU - Larson, MG

AU - Mooser, V

AU - Hadley, D

AU - Dorr, M

AU - Bis, JC

AU - Aspelund, T

AU - Esko, T

AU - Janssens, Cecile

AU - Zhao, JH

AU - Heath, S

AU - Laan, M

AU - Fu, JY

AU - Pistis, G

AU - Luan, JA

AU - Arora, M

AU - Lucas, G

AU - Pirastu, N

AU - Pichler, I

AU - Jackson, AU

AU - Webster, RJ

AU - Zhang, F

AU - Peden, JF

AU - Schmidt, Heléna

AU - Tanaka, T

AU - Campbell, H

AU - Igl, W

AU - Milaneschi, Y

AU - Hottenga, JJ (Jouke Jan)

AU - Vitart, V

AU - Chasman, DI

AU - Trompet, S

AU - Bragg-Gresham, JL

AU - Alizadeh, BZ

AU - Chambers, JC

AU - Guo, XQ

AU - Lehtimaki, T

AU - Kuhnel, B

AU - Lopez, LM

AU - Polasek, O

AU - Boban, M

AU - Nelson, CP

AU - Morrison, AC

AU - Pihur, V

AU - Ganesh, SK

AU - Hofman, Bert

AU - Kundu, Suman

AU - Mattace Raso, F.U.S.

AU - Rivadeneira, Fernando

AU - Sijbrands, E.J.G.

AU - Uitterlinden, André

AU - Hwang, SJ

AU - Vasan, RS

AU - Wang, TJ

AU - Bergmann, S

AU - Vollenweider, P

AU - Waeber, G

AU - Laitinen, J

AU - Pouta, A

AU - Zitting, P

AU - McArdle, WL

AU - Kroemer, HK

AU - Volker, U

AU - Volzke, H

AU - Glazer, NL

AU - Taylor, KD

AU - Harris, TB

AU - Alavere, H

AU - Haller, T

AU - Keis, A

AU - Tammesoo, ML

AU - Aulchenko, Yuriy

AU - Barroso, I

AU - Khaw, KT

AU - Galan, P

AU - Hercberg, S

AU - Lathrop, M

AU - Eyheramendy, S

AU - Org, E

AU - Sober, S

AU - Lu, XW

AU - Nolte, IM (Ilja)

AU - Penninx, BW

AU - Corre, T

AU - Masciullo, C

AU - Sala, C

AU - Groop, L

AU - Voight, BF

AU - Melander, O

AU - O'Donnell, CJ

AU - Salomaa, V

AU - d'Adamo, AP

AU - Fabretto, A

AU - Faletra, F

AU - Ulivi, S

AU - Del Greco, MF

AU - Facheris, M

AU - Collins, FS

AU - Bergman, RN

AU - Beilby, JP

AU - Hung, J

AU - Musk, AW

AU - Mangino, M

AU - Shin, SY

AU - Soranzo, N

AU - Watkins, H

AU - Goel, A

AU - Hamsten, A

AU - Gider, P

AU - Loitfelder, M

AU - Zeginigg, M

AU - Hernandez, D

AU - Najjar, SS

AU - Navarro, P

AU - Wild, SH

AU - Corsi, AM

AU - Singleton, A

AU - de Geus, EJC

AU - Willemsen, G

AU - Parker, AN

AU - Rose, LM

AU - Buckley, B

AU - Stott, D

AU - Orru, M

AU - Uda, M

AU - van der Klauw, MM (Melanie)

AU - Zhang, WH

AU - Li, XZ

AU - Scott, J

AU - Chen, YDI

AU - Burke, GL

AU - Kahonen, M

AU - Viikari, J

AU - Doring, A

AU - Meitinger, T

AU - Davies, G

AU - Starr, JM

AU - Emilsson, V

AU - Plump, A

AU - Lindeman, JH

AU - 't Hoen, PAC

AU - Konig, IR

AU - Felix, Janine

AU - Clarke, R

AU - Hopewell, JC

AU - Ongen, H

AU - Breteler, Monique

AU - Debette, S

AU - DeStefano, AL

AU - Fornage, M

AU - Mitchell, GF

AU - Smith, NL

AU - Holm, H

AU - Stefansson, K

AU - Thorleifsson, G

AU - Thorsteinsdottir, U

AU - Samani, NJ

AU - Preuss, M

AU - Rudan, I

AU - Hayward, C

AU - Deary, IJ

AU - Wichmann, HE

AU - Raitakari, OT

AU - Palmas, W

AU - Kooner, JS

AU - Stolk, RP (Ronald)

AU - Jukema, JW

AU - Wright, AF

AU - Boomsma, DI

AU - Bandinelli, S

AU - Gyllensten, UB

AU - Wilson, JF

AU - Ferrucci, L

AU - Schmidt, R

AU - Farrall, M

AU - Spector, TD

AU - Palmer, LJ

AU - Tuomilehto, J

AU - Pfeufer, A

AU - Gasparini, P

AU - Siscovick, D

AU - Altshuler, D

AU - Loos, RJF

AU - Toniolo, D

AU - Snieder, H

AU - Gieger, C

AU - Meneton, P

AU - Wareham, NJ

AU - Oostra, Ben

AU - Metspalu, A

AU - Launer, L

AU - Rettig, R

AU - Strachan, DP

AU - Beckmann, JS

AU - Witteman, JCM

AU - Erdmann, J

AU - van Dijk, KW

AU - Boerwinkle, E

AU - Boehnke, M

AU - Ridker, PM

AU - Jarvelin, MR

AU - Chakravarti, A

AU - Abecasis, GR

AU - Gudnason, V

AU - Newton-Cheh, C

AU - Levy, D

AU - Munroe, PB

AU - Psaty, BM

AU - Caulfield, MJ

AU - Rao, DC

AU - Tobin, MD

AU - Elliott, P

AU - Duijn, Cornelia

PY - 2011

Y1 - 2011

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.

U2 - 10.1038/ng.922

DO - 10.1038/ng.922

M3 - Article

C2 - 21909110

SN - 1061-4036

VL - 43

SP - 1005-U122

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -