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

Title: Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
Authors: 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
Item Type: Journal Article
Abstract: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans1,2,3. 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 × 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.
Issue Date: 11-Sep-2011
Date of Acceptance: 4-Aug-2011
URI: http://hdl.handle.net/10044/1/61810
DOI: https://dx.doi.org/10.1038/ng.922
ISSN: 1061-4036
Publisher: NATURE PUBLISHING GROUP
Start Page: 1005
End Page: U122
Journal / Book Title: NATURE GENETICS
Volume: 43
Issue: 10
Copyright Statement: © 2011 Nature America, Inc. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/ng.922
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: G0700931
G0601966
G0801056B
G0801056
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
ADRENERGIC-RECEPTOR TRAFFICKING
CARDIOVASCULAR-DISEASE RISK
BLOOD-PRESSURE
HEART-FAILURE
HYPERTENSION
METAANALYSIS
MORTALITY
GENE
MICE
RELEVANCE
Arteries
Blood Pressure
Case-Control Studies
Follow-Up Studies
Genetic Loci
Genome-Wide Association Study
Humans
Hypertension
Linkage Disequilibrium
Polymorphism, Single Nucleotide
LifeLines Cohort Study
EchoGen consortium
AortaGen Consortium
CHARGE Consortium Heart Failure Working Group
KidneyGen consortium
CKDGen consortium
Cardiogenics consortium
CardioGram
11 Medical And Health Sciences
06 Biological Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2011-09-11
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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