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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
| Publication available at: | https://www.repository.cam.ac.uk/handle/1810/256330 |
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| 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: | Department of Surgery and Cancer |
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