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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Title: The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Authors: Ehret, GB
Ferreira, T
Chasman, DI
Jackson, AU
Schmidt, EM
Johnson, T
Thorleifsson, G
Luan, J
Donnelly, LA
Kanoni, S
Petersen, AK
Pihur, V
Strawbridge, RJ
Shungin, D
Hughes, MF
Meirelles, O
Kaakinen, M
Bouatia-Naji, N
Kristiansson, K
Shah, S
Kleber, ME
Guo, X
Lyytikäinen, LP
Fava, C
Eriksson, N
Nolte, IM
Magnusson, PK
Salfati, EL
Rallidis, LS
Theusch, E
Smith, AJ
Folkersen, L
Witkowska, K
Pers, TH
Joehanes, R
Kim, SK
Lataniotis, L
Jansen, R
Johnson, AD
Warren, H
Kim, YJ
Zhao, W
Wu, Y
Tayo, BO
Bochud, M
CHARGE-EchoGen Consortium
CHARGE-HF Consortium
Wellcome Trust Case Control Consortium
Absher, D
Adair, LS
Amin, N
Arking, DE
Axelsson, T
Baldassarre, D
Balkau, B
Bandinelli, S
Barnes, MR
Barroso, I
Bevan, S
Bis, JC
Bjornsdottir, G
Boehnke, M
Boerwinkle, E
Bonnycastle, LL
Boomsma, DI
Bornstein, SR
Brown, MJ
Burnier, M
Cabrera, CP
Chambers, JC
Chang, IS
Cheng, CY
Chines, PS
Chung, RH
Collins, FS
Connell, JM
Döring, A
Dallongeville, J
Danesh, J
De Faire, U
Delgado, G
Dominiczak, AF
Doney, AS
Drenos, F
Edkins, S
Eicher, JD
Elosua, R
Enroth, S
Erdmann, J
Eriksson, P
Esko, T
Evangelou, E
Evans, A
Fall, T
Farrall, M
Felix, JF
Ferrières, J
Ferrucci, L
Fornage, M
Forrester, T
Franceschini, N
Franco, OH
Franco-Cereceda, A
Fraser, RM
Ganesh, SK
Gao, H
Gertow, K
Gianfagna, F
Gigante, B
Giulianini, F
Goel, A
Goodall, AH
Goodarzi, MO
Gorski, M
Gräßler, J
Groves, CJ
Gudnason, V
Gyllensten, U
Hallmans, G
Hartikainen, AL
Hassinen, M
Havulinna, AS
Hayward, C
Hercberg, S
Herzig, KH
Hicks, AA
Hingorani, AD
Hirschhorn, JN
Hofman, A
Holmen, J
Holmen, OL
Hottenga, JJ
Howard, P
Hsiung, CA
Hunt, SC
Ikram, MA
Illig, T
Iribarren, C
Jensen, RA
Kähönen, M
Kang, HM
Kathiresan, S
Keating, BJ
Khaw, KT
Kim, YK
Kim, E
Kivimaki, M
Klopp, N
Kolovou, G
Komulainen, P
Kooner, JS
Kosova, G
Krauss, RM
Kuh, D
Kutalik, Z
Kuusisto, J
Kvaløy, K
Lakka, TA
Lee, NR
Lee, IT
Lee, WJ
Levy, D
Li, X
Liang, KW
Lin, H
Lin, L
Lindström, J
Lobbens, S
Männistö, S
Müller, G
Müller-Nurasyid, M
Mach, F
Markus, HS
Marouli, E
McCarthy, MI
McKenzie, CA
Meneton, P
Menni, C
Metspalu, A
Mijatovic, V
Moilanen, L
Montasser, ME
Morris, AD
Morrison, AC
Mulas, A
Nagaraja, R
Narisu, N
Nikus, K
O'Donnell, CJ
O'Reilly, PF
Ong, KK
Paccaud, F
Palmer, CD
Parsa, A
Pedersen, NL
Penninx, BW
Perola, M
Peters, A
Poulter, N
Pramstaller, PP
Psaty, BM
Quertermous, T
Rao, DC
Rasheed, A
Rayner, NW
Renström, F
Rettig, R
Rice, KM
Roberts, R
Rose, LM
Rossouw, J
Samani, NJ
Sanna, S
Saramies, J
Schunkert, H
Sebert, S
Sheu, WH
Shin, YA
Sim, X
Smit, JH
Smith, AV
Sosa, MX
Spector, TD
Stančáková, A
Stanton, AV
Stirrups, KE
Stringham, HM
Sundstrom, J
Swift, AJ
Syvänen, AC
Tai, ES
Tanaka, T
Tarasov, KV
Teumer, A
Thorsteinsdottir, U
Tobin, MD
Tremoli, E
Uitterlinden, AG
Uusitupa, M
Vaez, A
Vaidya, D
Van Duijn, CM
Van Iperen, EP
Vasan, RS
Verwoert, GC
Virtamo, J
Vitart, V
Voight, BF
Vollenweider, P
Wagner, A
Wain, LV
Wareham, NJ
Watkins, H
Weder, AB
Westra, HJ
Wilks, R
Wilsgaard, T
Wilson, JF
Wong, TY
Yang, TP
Yao, J
Yengo, L
Zhang, W
Zhao, JH
Zhu, X
Bovet, P
Cooper, RS
Mohlke, KL
Saleheen, D
Lee, JY
Elliott, P
Gierman, HJ
Willer, CJ
Franke, L
Hovingh, GK
Taylor, KD
Dedoussis, G
Sever, P
Wong, A
Lind, L
Assimes, TL
Njølstad, I
Schwarz, PE
Langenberg, C
Snieder, H
Caulfield, MJ
Melander, O
Laakso, M
Saltevo, J
Rauramaa, R
Tuomilehto, J
Ingelsson, E
Lehtimäki, T
Hveem, K
Palmas, W
März, W
Kumari, M
Salomaa, V
Chen, YI
Rotter, JI
Froguel, P
Jarvelin, MR
Lakatta, EG
Kuulasmaa, K
Franks, PW
Hamsten, A
Wichmann, HE
Palmer, CN
Stefansson, K
Ridker, PM
Loos, RJ
Chakravarti, A
Deloukas, P
Morris, AP
Newton-Cheh, C
Munroe, PB
Item Type: Journal Article
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Issue Date: 12-Sep-2016
Date of Acceptance: 15-Aug-2016
URI: http://hdl.handle.net/10044/1/48175
DOI: https://dx.doi.org/10.1038/ng.3667
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 1171
End Page: 1184
Journal / Book Title: Nature Genetics
Volume: 48
Copyright Statement: © 2016 Nature America, Inc. All rights reserved.
Sponsor/Funder: National Institute for Health Research
Medical Research Council (MRC)
Funder's Grant Number: NF-SI-0611-10136
MR/L01341X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
ARTERIAL-HYPERTENSION
COMMON VARIANTS
CELL-TYPES
LOCI
TRAITS
CHROMATIN
SUSCEPTIBILITY
METAANALYSIS
BIOLOGY
African Continental Ancestry Group
Asian Continental Ancestry Group
Blood Pressure
Cells, Cultured
Genome-Wide Association Study
Humans
Hypertension
Microarray Analysis
Polymorphism, Single Nucleotide
CHARGE-EchoGen Consortium
CHARGE-HF Consortium
Wellcome Trust Case Control Consortium
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Epidemiology, Public Health and Primary Care



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