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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Title: Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
Authors: Surendran, P
Drenos, F
Young, R
Warren, H
Cook, JP
Manning, AK
Grarup, N
Sim, X
Barnes, DR
Witkowska, K
Staley, JR
Virtamo, J
Deloukas, P
Wellcome Trust Case Control Consortium
Elliott, P
Understanding Society Scientific Group
Zeggini, E
Kathiresan, S
Melander, O
Kuusisto, J
Harakalova, M
Lindström, J
Laakso, M
Padmanabhan, S
Porteous, DJ
Hayward, C
Scotland, G
Collins, FS
Mohlke, KL
Hansen, T
Pedersen, O
Boehnke, M
Uusitupa, M
Mihailov, E
Stringham, HM
EPIC-CVD Consortium
Frossard, P
Newton-Cheh, C
CHARGE+ Exome Chip Blood Pressure Consortium
Tobin, MD
Nordestgaard, BG
T2D-GENES Consortium
GoT2DGenes Consortium
Komulainen, P
ExomeBP Consortium
Liu, C
CHD Exome+ Consortium
Caulfield, MJ
Mahajan, A
Morris, AP
Tomaszewski, M
Samani, NJ
Saleheen, D
Asselbergs, FW
Lakka, TA
Lindgren, CM
Danesh, J
Kraja, AT
Wain, LV
Butterworth, AS
Howson, JM
Munroe, PB
Nielsen, SF
Rasheed, A
Samuel, M
Rauramaa, R
Zhao, W
Bonnycastle, LL
Jackson, AU
Narisu, N
Swift, AJ
Southam, L
Marten, J
Huyghe, JR
Stančáková, A
Fava, C
Polasek, O
Ohlsson, T
Matchan, A
Stirrups, KE
Bork-Jensen, J
Gjesing, AP
Kontto, J
Perola, M
Shaw-Hawkins, S
Havulinna, AS
Zhang, H
Rudan, I
Donnelly, LA
Groves, CJ
Rayner, NW
Neville, MJ
Robertson, NR
Yiorkas, AM
Herzig, KH
Kajantie, E
Zhang, W
Willems, SM
Rolandsson, O
Lannfelt, L
Malerba, G
Soranzo, N
Trabetti, E
Verweij, N
Evangelou, E
Moayyeri, A
Vergnaud, AC
Nelson, CP
Poveda, A
Franks, PW
Varga, TV
Caslake, M
De Craen, AJ
Trompet, S
Luan, J
Scott, RA
Harris, SE
Liewald, DC
Marioni, R
Menni, C
Dedoussis, G
Farmaki, AE
Hallmans, G
Renström, F
Huffman, JE
Hassinen, M
Burgess, S
Vasan, RS
Felix, JF
CHARGE-Heart Failure Consortium
Uria-Nickelsen, M
Tragante, V
Malarstig, A
Reilly, DF
Hoek, M
Vogt, TF
Lin, H
Lieb, W
EchoGen Consortium
Traylor, M
Markus, HS
METASTROKE Consortium
Spector, TD
Highland, HM
Justice, AE
Marouli, E
GIANT Consortium
EPIC-InterAct Consortium
Jousilahti, P
Männistö, S
Deary, IJ
Starr, JM
Langenberg, C
Wareham, NJ
Brown, MJ
Dominiczak, AF
Tukiainen, T
Connell, JM
Jukema, JW
Sattar, N
Ford, I
Packard, CJ
Esko, T
Mägi, R
Metspalu, A
De Boer, RA
Van der Meer, P
Yaghootkar, H
Van der Harst, P
Lifelines Cohort Study
Gambaro, G
Ingelsson, E
Lind, L
De Bakker, PI
Numans, ME
Brandslund, I
Christensen, C
Petersen, ER
Masca, N
Korpi-Hyövälti, E
Oksa, H
Chambers, JC
Kooner, JS
Blakemore, AI
Franks, S
Jarvelin, MR
Husemoen, LL
Linneberg, A
Skaaby, T
Freitag, DF
Thuesen, B
Karpe, F
Tuomilehto, J
Doney, AS
Morris, AD
Palmer, CN
Holmen, OL
Hveem, K
Willer, CJ
Tuomi, T
Ferreira, T
Groop, L
Käräjämäki, A
Palotie, A
Ripatti, S
Salomaa, V
Alam, DS
Majumder, AA
Di Angelantonio, E
Chowdhury, R
McCarthy, MI
Giannakopoulou, O
Poulter, N
Stanton, AV
Sever, P
Amouyel, P
Arveiler, D
Blankenberg, S
Ferrières, J
Kee, F
Kuulasmaa, K
Müller-Nurasyid, M
Tinker, A
Veronesi, G
Item Type: Journal Article
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Issue Date: 12-Sep-2016
Date of Acceptance: 2-Aug-2016
URI: http://hdl.handle.net/10044/1/40215
DOI: http://dx.doi.org/10.1038/ng.3654
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 1151
End Page: 1161
Journal / Book Title: Nature Genetics
Volume: 48
Sponsor/Funder: British Heart Foundation
Home Office
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
National Institute for Health Research
Action on Hearing Loss
Medical Research Council (MRC)
Funder's Grant Number: SP/04/02
PG0484
G0700931
084723/Z/08/Z
G0601966
NF-SI-0611-10136
G51_Chambers
MR/L01341X/1
Keywords: CHARGE-Heart Failure Consortium
EchoGen Consortium
METASTROKE Consortium
GIANT Consortium
EPIC-InterAct Consortium
Lifelines Cohort Study
Wellcome Trust Case Control Consortium
Understanding Society Scientific Group
EPIC-CVD Consortium
CHARGE+ Exome Chip Blood Pressure Consortium
T2D-GENES Consortium
GoT2DGenes Consortium
ExomeBP Consortium
CHD Exome+ Consortium
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Open Access location: https://www.repository.cam.ac.uk/handle/1810/256330
Appears in Collections:Division of Surgery
National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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