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

2016; Nature Portfolio; Volume: 48; Issue: 10 Linguagem: Inglês

10.1038/ng.3654

1546-1718

Praveen Surendran, Fotios Drenos, Robin Young, Helen R. Warren, James P. Cook, Alisa K. Manning, Niels Grarup, Xueling Sim, Daniel R. Barnes, Kate Witkowska, James R Staley, Vinicius Tragante, Taru Tukiainen, Hanieh Yaghootkar, Nicholas G. D. Masca, Daniel F. Freitag, Teresa Ferreira, Olga Giannakopoulou, Andrew Tinker, Magdaléna Harakaľová, Evelin Mihailov, Chunyu Liu, Aldi T. Kraja, Yan V. Sun, Asif Rasheed, Maria Samuel, Wei Zhao, Lori L. Bonnycastle, Anne Jackson, Narisu Narisu, Amy J. Swift, Lorraine Southam, Jonathan Marten, Jeroen R. Huyghe, Alena Stančáková, Cristiano Fava, Therese Ohlsson, Angela Matchan, Kathleen Stirrups, Jette Bork‐Jensen, Anette P. Gjesing, Jukka Kontto, Markus Perola, Susan Shaw-Hawkins, Aki S. Havulinna, He Zhang, Louise A. Donnelly, Christopher J. Groves, Nigel W. Rayner, Matt J. Neville, Neil R. Robertson, Andrianos M. Yiorkas, Karl‐Heinz Herzig, Eero Kajantie, Weihua Zhang, Sara M. Willems, Lars Lannfelt, Giovanni Malerba, Nicole Soranzo, Elisabetta Trabetti, Niek Verweij, Εvangelos Εvangelou, Alireza Moayyeri, Anne‐Claire Vergnaud, Christopher P. Nelson, Alaitz Poveda, Tibor V. Varga, Muriel Caslake, Anton J. M. de Craen, Stella Trompet, Jian’an Luan, Robert A. Scott, Sarah E. Harris, David C. Liewald, Riccardo E. Marioni, Cristina Menni, Aliki-Eleni Farmaki, Göran Hallmans, Frida Renström, Jennifer E. Huffman, Maija Hassinen, Stephen Burgess, Ramachandran S. Vasan, Janine F. Felix, Maria Uria-Nickelsen, Anders Mälarstig, Dermot F. Reilly, Maarten Hoek, Thomas Vogt, Honghuang Lin, Wolfgang Lieb, Matthew Traylor, Hugh S. Markus, Heather M. Highland, Anne E. Justice, Eirini Marouli, Jaana Lindström, Matti Uusitupa, Pirjo Komulainen, Timo A. Lakka, Rainer Rauramaa, Ozren Polašek, Igor Rudan, Olov Rolandsson, Paul W. Franks, George Dedoussis, Timothy D. Spector, Jari Lahti, Satu Männistö, Ian J. Deary, John M. Starr, Claudia Langenberg, Nicholas J. Wareham, Morris J. Brown, Anna F. Dominiczak, John Connell, J. Wouter Jukema, Naveed Sattar, Ian Ford, Chris J. Packard, Tõnu Esko, Reedik Mägi, Andres Metspalu, Rudolf A. de Boer, Peter van der Meer, Pim van der Harst, Giovanni Gambaro, Erik Ingelsson, Lars Lind, Paul I. W. de Bakker, Mattijs E. Numans, Ivan Brandslund, Cramer Christensen, Annette Peters, Eeva Korpi-Hyövälti, Heikki Oksa, John C. Chambers, Jaspal S. Kooner, Alexandra I. F. Blakemore, Steve Franks, Marjo‐Riitta Järvelin, Lise Lotte N. Husemoen, Allan Linneberg, Tea Skaaby, Betina H. Thuesen, Fredrik Karpe, Jaakko Tuomilehto, Alex S. F. Doney, Andrew D. Morris, Nicholette D. Palmer, Oddgeir L. Holmen, Kristian Hveem, Cristen J. Willer, Jaakko Tuomilehto, Leif Groop, Annemari Käräjämäki, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Dewan S Alam, Abdulla al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Mark I. McCarthy, Neil R Poulter, Alice Stanton, Peter Sever, Philippe Amouyel, Dominique Arveiler, Stefan Blankenberg, Jean Ferrières, Frank Kee, Kari Kuulasmaa, Martina Müller‐Nurasyid, Giovanni Veronesi, Jarmo Virtamo, Panos Deloukas, Paul Elliott, Eleftheria Zeggini, Sekar Kathiresan, Olle Melander, Johanna Kuusisto, Markku Laakso, Sandosh Padmanabhan, David J. Porteous, Caroline Hayward, Generation Scotland, Francis S. Collins, Karen L. Mohlke, Torben Hansen, Oluf Pedersen, Michael Boehnke, Heather M. Stringham, Philippe Frossard, Christopher Newton‐Cheh, Martin D. Tobin, Børge G. Nordestgaard, Mark J. Caulfield, Anubha Mahajan, Andrew P. Morris, Maciej Tomaszewski, Nilesh J. Samani, Danish Saleheen, Folkert W. Asselbergs, Cecilia M. Lindgren, John Danesh, Louise V. Wain, Adam S. Butterworth, Joanna M. M. Howson, Patricia B. Munroe,

Epigenetics and DNA Methylation

Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure– or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention. 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 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure– or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/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.