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; John C. Chambers; Xiuqing Guo; Terho Lehtimaki; Brigitte Kuehnel; Lorna M. Lopez; Ozren Polasek; Mladen Boban; Christopher P. Nelson; Alanna C. Morrison; Vasyl Pihur; Santhi K. Ganesh; Albert Hofman; Suman Kundu; Francesco U. S. Mattace-Raso; Fernando Rivadeneira; Eric J. G. Sijbrands; Andre G. Uitterlinden; Shih-Jen Hwang; Ramachandran S. Vasan; Thomas J. Wang; Sven Bergmann; Peter Vollenweider; Gerard Waeber; Jaana Laitinen; Anneli Pouta; Paavo Zitting; Wendy L. McArdle; Heyo K. Kroemer; Uwe Voelker; Henry Voelzke; Nicole L. Glazer; Kent D. Taylor; Tamara B. Harris; Helene Alavere; Toomas Haller; Aime Keis; Mari-Liis Tammesoo; Yurii Aulchenko; Ines Barroso; Kay-Tee Khaw; Pilar Galan; Serge Hercberg; Mark Lathrop; Susana Eyheramendy; Elin Org; Siim Sober; Xiaowen Lu; Ilja M. Nolte; Brenda W. Penninx; Tanguy Corre; Corrado Masciullo; Cinzia Sala; Leif Groop; Benjamin F. Voight; Olle Melander; Christopher J. O'Donnell; Veikko Salomaa; Adamo Pio d'Adamo; Antonella Fabretto; Flavio Faletra; Sheila Ulivi; Fabiola M. Del Greco; Maurizio Facheris; Francis S. Collins; Richard N. Bergman; John P. Beilby; Joseph Hung; A. William Musk; Massimo Mangino; So-Youn Shin; Nicole Soranzo; Hugh Watkins; Anuj Goel; Anders Hamsten; Pierre Gider; Marisa Loitfelder; Marion Zeginigg; Dena Hernandez; Samer S. Najjar; Pau Navarro; Sarah H. Wild; Anna Maria Corsi; Andrew Singleton; Eco J. C. de Geus; Gonneke Willemsen; Alex N. Parker; Lynda M. Rose; Brendan Buckley; David Stott; Marco Orru; Manuela Uda; Melanie M. van der Klauw; Weihua Zhang; Xinzhong Li; James Scott; Yii-Der Ida Chen; Gregory L. Burke; Mika Kahonen; Jorma Viikari; Angela Doering; Thomas Meitinger; Gail Davies; John M. Starr; Valur Emilsson; Andrew Plump; Jan H. Lindeman; Peter A. C. 't Hoen; Inke R. Koenig; Janine F. Felix; Robert Clarke; Jemma C. Hopewell; Halit Ongen; Monique Breteler; Stephanie Debette; Anita L. DeStefano; Myriam Fornage; Gary F. Mitchell; Nicholas L. Smith; Hilma Holm; Kari Stefansson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Nilesh J. Samani; Michael Preuss; Igor Rudan; Caroline Hayward; Ian J. Deary; H-Erich Wichmann; Olli T. Raitakari; Walter Palmas; Jaspal S. Kooner; Ronald P. Stolk; J. Wouter Jukema; Alan F. Wright; Dorret I. Boomsma; Stefania Bandinelli; Ulf B. Gyllensten; James F. Wilson; Luigi Ferrucci; Reinhold Schmidt; Martin Farrall; Tim D. Spector; Lyle J. Palmer; Jaakko Tuomilehto; Arne Pfeufer; Paolo Gasparini; David Siscovick; David Altshuler; Ruth J. F. Loos; Daniela Toniolo; Harold Snieder; Christian Gieger; Pierre Meneton; Nicholas J. Wareham; Ben A. Oostra; Andres Metspalu; Lenore Launer; Rainer Rettig; David P. Strachan; Jacques S. Beckmann; Jacqueline C. M. Witteman; Jeanette Erdmann; Ko Willems van Dijk; Eric Boerwinkle; Michael Boehnke; Paul M. Ridker; Marjo-Riitta Jarvelin; Aravinda Chakravarti; Goncalo R. Abecasis; Vilmundur Gudnason; Christopher Newton-Cheh; Daniel Levy; Patricia B. Munroe; Bruce M. Psaty; Mark J. Caulfield; Dabeeru C. Rao; Martin D. Tobin; Paul Elliott; Cornelia M. van Duijn

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, John C. Chambers, Xiuqing Guo, Terho Lehtimaki, Brigitte Kuehnel, Lorna M. Lopez, Ozren Polasek, Mladen Boban, Christopher P. Nelson, Alanna C. Morrison, Vasyl Pihur, Santhi K. Ganesh, Albert Hofman, Suman Kundu, Francesco U. S. Mattace-Raso, Fernando Rivadeneira, Eric J. G. Sijbrands, Andre G. Uitterlinden, Shih-Jen Hwang, Ramachandran S. Vasan, Thomas J. Wang, Sven Bergmann, Peter Vollenweider, Gerard Waeber, Jaana Laitinen, Anneli Pouta, Paavo Zitting, Wendy L. McArdle, Heyo K. Kroemer, Uwe Voelker, Henry Voelzke, Nicole L. Glazer, Kent D. Taylor, Tamara B. Harris, Helene Alavere, Toomas Haller, Aime Keis, Mari-Liis Tammesoo, Yurii Aulchenko, Ines Barroso, Kay-Tee Khaw, Pilar Galan, Serge Hercberg, Mark Lathrop, Susana Eyheramendy, Elin Org, Siim Sober, Xiaowen Lu, Ilja M. Nolte, Brenda W. Penninx, Tanguy Corre, Corrado Masciullo, Cinzia Sala, Leif Groop, Benjamin F. Voight, Olle Melander, Christopher J. O'Donnell, Veikko Salomaa, Adamo Pio d'Adamo, Antonella Fabretto, Flavio Faletra, Sheila Ulivi, Fabiola M. Del Greco, Maurizio Facheris, Francis S. Collins, Richard N. Bergman, John P. Beilby, Joseph Hung, A. William Musk, Massimo Mangino, So-Youn Shin, Nicole Soranzo, Hugh Watkins, Anuj Goel, Anders Hamsten, Pierre Gider, Marisa Loitfelder, Marion Zeginigg, Dena Hernandez, Samer S. Najjar, Pau Navarro, Sarah H. Wild, Anna Maria Corsi, Andrew Singleton, Eco J. C. de Geus, Gonneke Willemsen, Alex N. Parker, Lynda M. Rose, Brendan Buckley, David Stott, Marco Orru, Manuela Uda, Melanie M. van der Klauw, Weihua Zhang, Xinzhong Li, James Scott, Yii-Der Ida Chen, Gregory L. Burke, Mika Kahonen, Jorma Viikari, Angela Doering, Thomas Meitinger, Gail Davies, John M. Starr, Valur Emilsson, Andrew Plump, Jan H. Lindeman, Peter A. C. 't Hoen, Inke R. Koenig, Janine F. Felix, Robert Clarke, Jemma C. Hopewell, Halit Ongen, Monique Breteler, Stephanie Debette, Anita L. DeStefano, Myriam Fornage, Gary F. Mitchell, Nicholas L. Smith, Hilma Holm, Kari Stefansson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Nilesh J. Samani, Michael Preuss, Igor Rudan, Caroline Hayward, Ian J. Deary, H-Erich Wichmann, Olli T. Raitakari, Walter Palmas, Jaspal S. Kooner, Ronald P. Stolk, J. Wouter Jukema, Alan F. Wright, Dorret I. Boomsma, Stefania Bandinelli, Ulf B. Gyllensten, James F. Wilson, Luigi Ferrucci, Reinhold Schmidt, Martin Farrall, Tim D. Spector, Lyle J. Palmer, Jaakko Tuomilehto, Arne Pfeufer, Paolo Gasparini, David Siscovick, David Altshuler, Ruth J. F. Loos, Daniela Toniolo, Harold Snieder, Christian Gieger, Pierre Meneton, Nicholas J. Wareham, Ben A. Oostra, Andres Metspalu, Lenore Launer, Rainer Rettig, David P. Strachan, Jacques S. Beckmann, Jacqueline C. M. Witteman, Jeanette Erdmann, Ko Willems van Dijk, Eric Boerwinkle, Michael Boehnke, Paul M. Ridker, Marjo-Riitta Jarvelin, Aravinda Chakravarti, Goncalo R. Abecasis, Vilmundur Gudnason, Christopher Newton-Cheh, Daniel Levy, Patricia B. Munroe, Bruce M. Psaty, Mark J. Caulfield, Dabeeru C. Rao, Martin D. Tobin, Paul Elliott, Cornelia M. van Duijn

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

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
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.922
Publication status	Published - 2011

Subject classification (UKÄ)

Cardiac and Cardiovascular Systems
Endocrinology and Diabetes

UN SDGs

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

Access to Document

10.1038/ng.922

Cite this

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., ... van Duijn, C. M. (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{2c9cfbd817314ef78ae6dd5e46c528a2,

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 = "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 Chambers, {John C.} and Xiuqing Guo and Terho Lehtimaki and Brigitte Kuehnel and Lopez, {Lorna M.} and Ozren Polasek and Mladen Boban and Nelson, {Christopher P.} and Morrison, {Alanna C.} and Vasyl Pihur and Ganesh, {Santhi K.} and Albert Hofman and Suman Kundu and Mattace-Raso, {Francesco U. S.} and Fernando Rivadeneira and Sijbrands, {Eric J. G.} and Uitterlinden, {Andre G.} and Shih-Jen Hwang and Vasan, {Ramachandran S.} and Wang, {Thomas J.} and Sven Bergmann and Peter Vollenweider and Gerard Waeber and Jaana Laitinen and Anneli Pouta and Paavo Zitting and McArdle, {Wendy L.} and Kroemer, {Heyo K.} and Uwe Voelker and Henry Voelzke and Glazer, {Nicole L.} and Taylor, {Kent D.} and Harris, {Tamara B.} and Helene Alavere and Toomas Haller and Aime Keis and Mari-Liis Tammesoo and Yurii Aulchenko and Ines Barroso and Kay-Tee Khaw and Pilar Galan and Serge Hercberg and Mark Lathrop and Susana Eyheramendy and Elin Org and Siim Sober and Xiaowen Lu and Nolte, {Ilja M.} and Penninx, {Brenda W.} and Tanguy Corre and Corrado Masciullo and Cinzia Sala and Leif Groop and Voight, {Benjamin F.} and Olle Melander and O'Donnell, {Christopher J.} and Veikko Salomaa and d'Adamo, {Adamo Pio} and Antonella Fabretto and Flavio Faletra and Sheila Ulivi and {Del Greco}, {Fabiola M.} and Maurizio Facheris and Collins, {Francis S.} and Bergman, {Richard N.} and Beilby, {John P.} and Joseph Hung and Musk, {A. William} and Massimo Mangino and So-Youn Shin and Nicole Soranzo and Hugh Watkins and Anuj Goel and Anders Hamsten and Pierre Gider and Marisa Loitfelder and Marion Zeginigg and Dena Hernandez and Najjar, {Samer S.} and Pau Navarro and Wild, {Sarah H.} and Corsi, {Anna Maria} and Andrew Singleton and {de Geus}, {Eco J. C.} and Gonneke Willemsen and Parker, {Alex N.} and Rose, {Lynda M.} and Brendan Buckley and David Stott and Marco Orru and Manuela Uda and {van der Klauw}, {Melanie M.} and Weihua Zhang and Xinzhong Li and James Scott and Chen, {Yii-Der Ida} and Burke, {Gregory L.} and Mika Kahonen and Jorma Viikari and Angela Doering and Thomas Meitinger and Gail Davies and Starr, {John M.} and Valur Emilsson and Andrew Plump and Lindeman, {Jan H.} and {'t Hoen}, {Peter A. C.} and Koenig, {Inke R.} and Felix, {Janine F.} and Robert Clarke and Hopewell, {Jemma C.} and Halit Ongen and Monique Breteler and Stephanie Debette and DeStefano, {Anita L.} and Myriam Fornage and Mitchell, {Gary F.} and Smith, {Nicholas L.} and Hilma Holm and Kari Stefansson and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Samani, {Nilesh J.} and Michael Preuss and Igor Rudan and Caroline Hayward and Deary, {Ian J.} and H-Erich Wichmann and Raitakari, {Olli T.} and Walter Palmas and Kooner, {Jaspal S.} and Stolk, {Ronald P.} and Jukema, {J. Wouter} and Wright, {Alan F.} and Boomsma, {Dorret I.} and Stefania Bandinelli and Gyllensten, {Ulf B.} and Wilson, {James F.} and Luigi Ferrucci and Reinhold Schmidt and Martin Farrall and Spector, {Tim D.} and Palmer, {Lyle J.} and Jaakko Tuomilehto and Arne Pfeufer and Paolo Gasparini and David Siscovick and David Altshuler and Loos, {Ruth J. F.} and Daniela Toniolo and Harold Snieder and Christian Gieger and Pierre Meneton and Wareham, {Nicholas J.} and Oostra, {Ben A.} and Andres Metspalu and Lenore Launer and Rainer Rettig and Strachan, {David P.} and Beckmann, {Jacques S.} and Witteman, {Jacqueline C. M.} and Jeanette Erdmann and {van Dijk}, {Ko Willems} and Eric Boerwinkle and Michael Boehnke and Ridker, {Paul M.} and Marjo-Riitta Jarvelin and Aravinda Chakravarti and Abecasis, {Goncalo R.} and Vilmundur Gudnason and Christopher Newton-Cheh and Daniel Levy and Munroe, {Patricia B.} and Psaty, {Bruce M.} and Caulfield, {Mark J.} and Rao, {Dabeeru C.} and Tobin, {Martin D.} and Paul Elliott and {van Duijn}, {Cornelia M.}",

year = "2011",

doi = "10.1038/ng.922",

language = "English",

volume = "43",

pages = "1005--U122",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Publishing Group",

number = "10",

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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, Chambers, JC, Guo, X, Lehtimaki, T, Kuehnel, B, Lopez, LM, Polasek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FUS, Rivadeneira, F, Sijbrands, EJG, Uitterlinden, AG, Hwang, S-J, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Voelker, U, Voelzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, M-L, Aulchenko, Y, Barroso, I, Khaw, K-T, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sober, S, Lu, X, 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, FM, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, S-Y, 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, W, Li, X, Scott, J, Chen, Y-DI, Burke, GL, Kahonen, M, Viikari, J, Doering, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, 't Hoen, PAC, Koenig, IR, Felix, JF, 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, H-E, 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, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JCM, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, M-R, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P & van Duijn, CM 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 - Chambers, John C.

AU - Guo, Xiuqing

AU - Lehtimaki, Terho

AU - Kuehnel, Brigitte

AU - Lopez, Lorna M.

AU - Polasek, Ozren

AU - Boban, Mladen

AU - Nelson, Christopher P.

AU - Morrison, Alanna C.

AU - Pihur, Vasyl

AU - Ganesh, Santhi K.

AU - Hofman, Albert

AU - Kundu, Suman

AU - Mattace-Raso, Francesco U. S.

AU - Rivadeneira, Fernando

AU - Sijbrands, Eric J. G.

AU - Uitterlinden, Andre G.

AU - Hwang, Shih-Jen

AU - Vasan, Ramachandran S.

AU - Wang, Thomas J.

AU - Bergmann, Sven

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Laitinen, Jaana

AU - Pouta, Anneli

AU - Zitting, Paavo

AU - McArdle, Wendy L.

AU - Kroemer, Heyo K.

AU - Voelker, Uwe

AU - Voelzke, Henry

AU - Glazer, Nicole L.

AU - Taylor, Kent D.

AU - Harris, Tamara B.

AU - Alavere, Helene

AU - Haller, Toomas

AU - Keis, Aime

AU - Tammesoo, Mari-Liis

AU - Aulchenko, Yurii

AU - Barroso, Ines

AU - Khaw, Kay-Tee

AU - Galan, Pilar

AU - Hercberg, Serge

AU - Lathrop, Mark

AU - Eyheramendy, Susana

AU - Org, Elin

AU - Sober, Siim

AU - Lu, Xiaowen

AU - Nolte, Ilja M.

AU - Penninx, Brenda W.

AU - Corre, Tanguy

AU - Masciullo, Corrado

AU - Sala, Cinzia

AU - Groop, Leif

AU - Voight, Benjamin F.

AU - Melander, Olle

AU - O'Donnell, Christopher J.

AU - Salomaa, Veikko

AU - d'Adamo, Adamo Pio

AU - Fabretto, Antonella

AU - Faletra, Flavio

AU - Ulivi, Sheila

AU - Del Greco, Fabiola M.

AU - Facheris, Maurizio

AU - Collins, Francis S.

AU - Bergman, Richard N.

AU - Beilby, John P.

AU - Hung, Joseph

AU - Musk, A. William

AU - Mangino, Massimo

AU - Shin, So-Youn

AU - Soranzo, Nicole

AU - Watkins, Hugh

AU - Goel, Anuj

AU - Hamsten, Anders

AU - Gider, Pierre

AU - Loitfelder, Marisa

AU - Zeginigg, Marion

AU - Hernandez, Dena

AU - Najjar, Samer S.

AU - Navarro, Pau

AU - Wild, Sarah H.

AU - Corsi, Anna Maria

AU - Singleton, Andrew

AU - de Geus, Eco J. C.

AU - Willemsen, Gonneke

AU - Parker, Alex N.

AU - Rose, Lynda M.

AU - Buckley, Brendan

AU - Stott, David

AU - Orru, Marco

AU - Uda, Manuela

AU - van der Klauw, Melanie M.

AU - Zhang, Weihua

AU - Li, Xinzhong

AU - Scott, James

AU - Chen, Yii-Der Ida

AU - Burke, Gregory L.

AU - Kahonen, Mika

AU - Viikari, Jorma

AU - Doering, Angela

AU - Meitinger, Thomas

AU - Davies, Gail

AU - Starr, John M.

AU - Emilsson, Valur

AU - Plump, Andrew

AU - Lindeman, Jan H.

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AU - Koenig, Inke R.

AU - Felix, Janine F.

AU - Clarke, Robert

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AU - Debette, Stephanie

AU - DeStefano, Anita L.

AU - Fornage, Myriam

AU - Mitchell, Gary F.

AU - Smith, Nicholas L.

AU - Holm, Hilma

AU - Stefansson, Kari

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

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AU - Preuss, Michael

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Deary, Ian J.

AU - Wichmann, H-Erich

AU - Raitakari, Olli T.

AU - Palmas, Walter

AU - Kooner, Jaspal S.

AU - Stolk, Ronald P.

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AU - Wright, Alan F.

AU - Boomsma, Dorret I.

AU - Bandinelli, Stefania

AU - Gyllensten, Ulf B.

AU - Wilson, James F.

AU - Ferrucci, Luigi

AU - Schmidt, Reinhold

AU - Farrall, Martin

AU - Spector, Tim D.

AU - Palmer, Lyle J.

AU - Tuomilehto, Jaakko

AU - Pfeufer, Arne

AU - Gasparini, Paolo

AU - Siscovick, David

AU - Altshuler, David

AU - Loos, Ruth J. F.

AU - Toniolo, Daniela

AU - Snieder, Harold

AU - Gieger, Christian

AU - Meneton, Pierre

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AU - Oostra, Ben A.

AU - Metspalu, Andres

AU - Launer, Lenore

AU - Rettig, Rainer

AU - Strachan, David P.

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AU - Witteman, Jacqueline C. M.

AU - Erdmann, Jeanette

AU - van Dijk, Ko Willems

AU - Boerwinkle, Eric

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AU - Ridker, Paul M.

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AU - Abecasis, Goncalo R.

AU - Gudnason, Vilmundur

AU - Newton-Cheh, Christopher

AU - Levy, Daniel

AU - Munroe, Patricia B.

AU - Psaty, Bruce M.

AU - Caulfield, Mark J.

AU - Rao, Dabeeru C.

AU - Tobin, Martin D.

AU - Elliott, Paul

AU - van Duijn, Cornelia M.

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 - 1546-1718

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

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