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PMID: 21909110 Published · epublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 43 ·No. 10 ·2011-09-11 ·Pages 1005-11

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 AC, 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 JJ, Vitart V, Chasman DI, Trompet S, Bragg-Gresham JL, Alizadeh BZ, Chambers JC, Guo X, Lehtimäki T, Kühnel B, Lopez LM, Polašek O, Boban M, Nelson CP, Morrison AC, Pihur V, Ganesh SK, Hofman A, Kundu S, Mattace-Raso FU, Rivadeneira F, Sijbrands EJ, Uitterlinden AG, Hwang SJ, Vasan RS, Wang TJ, Bergmann S, Vollenweider P, Waeber G, Laitinen J, Pouta A, Zitting P, McArdle WL, Kroemer HK, Völker U, Völzke 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, Sõber 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 F, 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 EJ, Willemsen G, Parker AN, Rose LM, Buckley B, Stott D, Orru M, Uda M, LifeLines Cohort Study, van der Klauw MM, Zhang W, Li X, Scott J, Chen YD, Burke GL, Kähönen M, Viikari J, Döring A, Meitinger T, Davies G, Starr JM, Emilsson V, Plump A, Lindeman JH, Hoen PA, König IR, EchoGen consortium, Felix JF, Clarke R, Hopewell JC, Ongen H, Breteler M, Debette S, Destefano AL, Fornage M, AortaGen Consortium, Mitchell GF, CHARGE Consortium Heart Failure Working Group, Smith NL, KidneyGen consortium, Holm H, Stefansson K, Thorleifsson G, Thorsteinsdottir U, CKDGen consortium, Cardiogenics consortium, CardioGram, 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 RJ, Toniolo D, Snieder H, Gieger C, Meneton P, Wareham NJ, Oostra BA, Metspalu A, Launer L, Rettig R, Strachan DP, Beckmann JS, Witteman JC, 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, van Duijn CM

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.

MeSH Terms
Arteries/metabolism Blood Pressure/genetics Case-Control Studies Follow-Up Studies Genetic Loci Genome-Wide Association Study Humans Hypertension/genetics Linkage Disequilibrium Polymorphism, Single Nucleotide
Authors & Affiliations
232 authors, click to expand affiliations / ORCID
Wain Louise V
Department of Health Sciences, University of Leicester, Leicester, UK.
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
Kühnel Brigitte
Lopez Lorna M
Polašek Ozren
Boban Mladen
Nelson Christopher P
Morrison Alanna C
Pihur Vasyl
Ganesh Santhi K
Hofman Albert
Kundu Suman
Mattace-Raso Francesco U S
Rivadeneira Fernando
Sijbrands Eric J G
Uitterlinden Andre G
Hwang Shih-Jen
Vasan Ramachandran S
Wang Thomas J
Bergmann Sven
Vollenweider Peter
Waeber Gérard
Laitinen Jaana
Pouta Anneli
Zitting Paavo
McArdle Wendy L
Kroemer Heyo K
Völker Uwe
Völzke Henry
Glazer Nicole L
Taylor Kent D
Harris Tamara B
Alavere Helene
Haller Toomas
Keis Aime
Tammesoo Mari-Liis
Aulchenko Yurii
Barroso Inês
Khaw Kay-Tee
Galan Pilar
Hercberg Serge
Lathrop Mark
Eyheramendy Susana
Org Elin
Sõber Siim
Lu Xiaowen
Nolte Ilja M
Penninx Brenda W
Corre Tanguy
Masciullo Corrado
Sala Cinzia
Groop Leif
Voight Benjamin F
Melander Olle
O'Donnell Christopher J
Salomaa Veikko
d'Adamo Adamo Pio
Fabretto Antonella
Faletra Flavio
Ulivi Sheila
Del Greco Fabiola M
Facheris Maurizio
Collins Francis S
Bergman Richard N
Beilby John P
Hung Joseph
Musk A William
Mangino Massimo
Shin So-Youn
Soranzo Nicole
Watkins Hugh
Goel Anuj
Hamsten Anders
Gider Pierre
Loitfelder Marisa
Zeginigg Marion
Hernandez Dena
Najjar Samer S
Navarro Pau
Wild Sarah H
Corsi Anna Maria
Singleton Andrew
de Geus Eco J C
Willemsen Gonneke
Parker Alex N
Rose Lynda M
Buckley Brendan
Stott David
Orru Marco
Uda Manuela
LifeLines Cohort Study
van der Klauw Melanie M
Zhang Weihua
Li Xinzhong
Scott James
Chen Yii-Der Ida
Burke Gregory L
Kähönen Mika
Viikari Jorma
Döring Angela
Meitinger Thomas
Davies Gail
Starr John M
Emilsson Valur
Plump Andrew
Lindeman Jan H
Hoen Peter A C 't
König Inke R
EchoGen consortium
Felix Janine F
Clarke Robert
Hopewell Jemma C
Ongen Halit
Breteler Monique
Debette Stéphanie
Destefano Anita L
Fornage Myriam
AortaGen Consortium
Mitchell Gary F
CHARGE Consortium Heart Failure Working Group
Smith Nicholas L
KidneyGen consortium
Holm Hilma
Stefansson Kari
Thorleifsson Gudmar
Thorsteinsdottir Unnur
CKDGen consortium
Cardiogenics consortium
CardioGram
Samani Nilesh J
Preuss Michael
Rudan Igor
Hayward Caroline
Deary Ian J
Wichmann H-Erich
Raitakari Olli T
Palmas Walter
Kooner Jaspal S
Stolk Ronald P
Jukema J Wouter
Wright Alan F
Boomsma Dorret I
Bandinelli Stefania
Gyllensten Ulf B
Wilson James F
Ferrucci Luigi
Schmidt Reinhold
Farrall Martin
Spector Tim D
Palmer Lyle J
Tuomilehto Jaakko
Pfeufer Arne
Gasparini Paolo
Siscovick David
Altshuler David
Loos Ruth J F
Toniolo Daniela
Snieder Harold
Gieger Christian
Meneton Pierre
Wareham Nicholas J
Oostra Ben A
Metspalu Andres
Launer Lenore
Rettig Rainer
Strachan David P
Beckmann Jacques S
Witteman Jacqueline C M
Erdmann Jeanette
van Dijk Ko Willems
Boerwinkle Eric
Boehnke Michael
Ridker Paul M
Jarvelin Marjo-Riitta
Chakravarti Aravinda
Abecasis Goncalo R
Gudnason Vilmundur
Newton-Cheh Christopher
Levy Daniel
Munroe Patricia B
Psaty Bruce M
Caulfield Mark J
Rao Dabeeru C
Tobin Martin D
Elliott Paul
van Duijn Cornelia M
Investigators
653 investigators, click to expand
McEniery Carmel M
Wilkinson Ian B
Cockcroft John R
O'Shaughnessy Kevin M
Newhouse Stephen J
Yasmin
Smith Albert V
Eiriksdottir Gudny
Launer Lenore J
Sigurdsson Sigurdur
Aspelund Thor
Gudnason Vilmundur
De Bacquer Dirk
Rietzschel Ernst R
De Backer Guy G
Van Bortel Luc
De Buyzere Marc L
Segers Patrick
Bekaert Sofie
Gillebert Thierry C
De Meyer Tim
Ferrucci Luigi
Tanaka Toshiko
Johnson Andrew D
Levy Daniel
Benjamin Emelia J
Mitchell Gary F
Vita Joseph A
Larson Martin G
Hamburg Naomi M
Vasan Ramachandran S
Isaacs Aaron
Schut Anna F C
Oostra Ben A
van Duijn Cornelia M
van Rijn Marie Josee E
Sie Mark P
Newman Anne B
Herrington David M
Andrews Jeanette S
Ding Jingzhong
Sutton-Tyrrell Kim C
Harris Tamara B
Howard Timothy D
Liu Yongmei
Parsa Afshin
Shuldiner Alan R
McArdle Patrick F
Gibson Quince
Post Wendy S
Dehghan Abbas
Hofman Albert
Uitterlinden André G
Sijbrands Eric J G
Rivadeneira Fernando
Mattace-Raso Francesco U S
Verwoert Germaine C
Witteman Jacqueline C M
Scuteri Angelo
Lakatta Edward G
Jewell Elizabeth
Abecasis Gonçalo R
Tarasov Kirill V
Uda Manuela
Najjar Samer S
Sanna Serena
Attwood Tony
Belz Stephanie
Braund Peter
Cambien François
Cooper Jason
Crisp-Hihn Abi
Deloukas Panos
Foad Nicola
Eardman Jeanette
Goodall Alison H
Gracey Jay
Gray Emma
Gulde Stefanie
Gwilliams Rhian
Heimerl Susanne
Hengstenberg Christian
Jolley Jennifer
Krishnan Unni
Linsel-Nitschke Patrick
Lloyd-Jones Heather
Lugauer Ingrid
Lundmark Per
Maouche Seraya
Moore Jasbir S
Muir David
Murray Elizabeth
Nelson Chris P
Neudert Jessica
Niblett David
O'Leary Karen
Ouwehand Willem H
Pollard Helen
Rankin Angela
Rice Catherine M
Sager Hendrik
Samani Nilesh J
Sambrook Jennifer
Schmitz Gerd
Scholz Michael
Schroeder Laura
Schunkert Heribert
Syvannen Ann-Christine
Wallace Chris
Kathiresan Sekar
Reilly Muredach P
Samani Nilesh J
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Erdmann Jeanette
Assimes Themistocles L
Boerwinkle Eric
Erdmann Jeanette
Hall Alistair
Hengstenberg Christian
Kathiresan Sekar
König Inke R
Laaksonen Reijo
McPherson Ruth
Reilly Muredach P
Samani Nilesh J
Schunkert Heribert
Thompson John R
Thorsteinsdottir Unnur
Ziegler Andreas
König Inke R
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Absher Devin
Chen Li
Cupples L Adrienne
Halperin Eran
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Voight Benjamin F
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McPherson Ruth
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Roberts Robert
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Schunkert Heribert
Stewart Alexandre F R
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Assimes Themistocles L
Fortmann Stephen
Go Alan
Hlatky Mark
Iribarren Carlos
Knowles Joshua
Myers Richard
Quertermous Thomas
Sidney Steven
Risch Neil
Tang Hua
Blankenberg Stefan
Zeller Tanja
Schillert Arne
Wild Philipp
Ziegler Andreas
Schnabel Renate
Sinning Christoph
Lackner Karl
Tiret Laurence
Nicaud Viviane
Cambien Francois
Bickel Christoph
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Perret Claire
Proust Carole
Münzel Thomas
Barbalic Maja
Bis Joshua
Boerwinkle Eric
Chen Ida Yii-Der
Cupples L Adrienne
Dehghan Abbas
Demissie-Banjaw Serkalem
Folsom Aaron
Glazer Nicole
Gudnason Vilmundur
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Heckbert Susan
Levy Daniel
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Marciante Kristin
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Psaty Bruce M
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van Duijn Cornelia
Volcik Kelly
Whitteman Jaqueline
Ramachandran Vasan
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Gretarsdottir Solveig
Gulcher Jeffrey R
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2011-09-11
Epub
2011-00-11
Pages
1005-11
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3445021
Subset
IM
Grants
Medical Research Council · G0801056 · United Kingdom
NHLBI NIH HHS · R01 HL043851 · United States
NHLBI NIH HHS · N01 HC025195 · United States
NHLBI NIH HHS · R01 HL086694 · United States
Medical Research Council · G1000143 · United Kingdom
Medical Research Council · MC_U106179471 · United Kingdom
Medical Research Council · MC_PC_U127592696 · United Kingdom
Medical Research Council · G0401527 · United Kingdom
NHLBI NIH HHS · N01 HC055015 · United States
Medical Research Council · G0902313 · United Kingdom
Medical Research Council · G0700704 · United Kingdom
NHLBI NIH HHS · N01 HC085079 · United States
Medical Research Council · MC_U106188470 · United Kingdom
NHLBI NIH HHS · K23 HL080025 · United States
Chief Scientist Office · ETM/55 · United Kingdom
Chief Scientist Office · CZB/4/505 · United Kingdom
Chief Scientist Office · CZB/4/710 · United Kingdom
Medical Research Council · G9521010 · United Kingdom
Medical Research Council · MC_U127561128 · United Kingdom
Medical Research Council · G0700931 · United Kingdom
Medical Research Council · MC_U137686857 · United Kingdom
Medical Research Council · G0601966 · United Kingdom
NHLBI NIH HHS · R01 HL105756 · United States
NIMHD NIH HHS · 263 MD9164 13 · United States
Intramural NIH HHS · Z01 HG000024-13 · United States
Medical Research Council · G0701863 · United Kingdom
Wellcome Trust · 090532 · United Kingdom
NIA NIH HHS · N01 AG012109 · United States
Medical Research Council · MC_PC_U127561128 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/F019394/1 · United Kingdom
Medical Research Council · MC_U127592696 · United Kingdom
NHLBI NIH HHS · U10 HL054512 · United States
NHLBI NIH HHS · N01 HC095159 · United States
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