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

Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P.; Manning, Alisa K.; Grarup, Niels; Sim, Xueling; Barnes, Daniel R. and Witkowska, Kate, et al. (2016) In Nature Genetics 48(10). p.1151-1161
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 192,763 individuals and used -1/4155,063 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... (More)

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 -1/4155,063 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.

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Nature Genetics
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48
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10
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11 pages
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Nature Publishing Group
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  • scopus:84987670072
  • wos:000384391600010
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1061-4036
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10.1038/ng.3654
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English
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2016-10-27 08:50:39
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@article{916bdc2c-1aae-4d2e-ae43-b0b6f891545c,
  abstract     = {<p>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 -1/4155,063 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 (&gt;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.</p>},
  author       = {Surendran, Praveen and Drenos, Fotios and Young, Robin and Warren, Helen and Cook, James P. and Manning, Alisa K. and Grarup, Niels and Sim, Xueling and Barnes, Daniel R. and Witkowska, Kate and Staley, James R. and Tragante, Vinicius and Tukiainen, Taru and Yaghootkar, Hanieh and Masca, Nicholas and Freitag, Daniel F. and Ferreira, Teresa and Giannakopoulou, Olga and Tinker, Andrew and Harakalova, Magdalena and Mihailov, Evelin and Liu, Chunyu and Kraja, Aldi T. and Nielsen, Sune Fallgaard and Rasheed, Asif and Samuel, Maria and Zhao, Wei and Bonnycastle, Lori L. and Jackson, Anne U. and Narisu, Narisu and Swift, Amy J. and Southam, Lorraine and Marten, Jonathan and Huyghe, Jeroen R. and Stančáková, Alena and Fava, Cristiano and Ohlsson, Therese and Matchan, Angela and Stirrups, Kathleen E. and Bork-Jensen, Jette and Gjesing, Anette P. and Kontto, Jukka and Perola, Markus and Shaw-Hawkins, Susan and Havulinna, Aki S. and Zhang, He and Donnelly, Louise A. and Groves, Christopher J. and Rayner, N. William and Neville, Matt J. and Robertson, Neil R. and Yiorkas, Andrianos M. and Herzig, Karl Heinz and Kajantie, Eero and Zhang, Weihua and Willems, Sara M. and Lannfelt, Lars and Malerba, Giovanni and Soranzo, Nicole and Trabetti, Elisabetta and Verweij, Niek and Evangelou, Evangelos and Moayyeri, Alireza and Vergnaud, Anne Claire and Nelson, Christopher P. and Poveda, Alaitz and Varga, Tibor V. and Caslake, Muriel and De Craen, Anton J M and Trompet, Stella and Luan, Jian'An and Scott, Robert A. and Harris, Sarah E. and Liewald, David C M and Marioni, Riccardo and Menni, Cristina and Farmaki, Aliki Eleni and Hallmans, Göran and Renström, Frida and Huffman, Jennifer E. and Hassinen, Maija and Burgess, Stephen and Vasan, Ramachandran S. and Felix, Janine F. and Uria-Nickelsen, Maria and Malarstig, Anders and Reilly, Dermot F. and Hoek, Maarten and Vogt, Thomas F. and Lin, Honghuang and Lieb, Wolfgang and Traylor, Matthew and Markus, Hugh S. and Highland, Heather M. and Justice, Anne E. and Marouli, Eirini and Lindström, Jaana and Uusitupa, Matti and Komulainen, Pirjo and Lakka, Timo A. and Rauramaa, Rainer and Polasek, Ozren and Rudan, Igor and Rolandsson, Olov and Franks, Paul W. and Dedoussis, George and Spector, Timothy D. and Jousilahti, Pekka and Männistö, Satu and Deary, Ian J. and Starr, John M. and Langenberg, Claudia and Wareham, Nick J. and Brown, Morris J. and Dominiczak, Anna F. and Connell, John M. and Jukema, J. Wouter and Sattar, Naveed and Ford, Ian and Packard, Chris J. and Esko, Tõnu and Mägi, Reedik and Metspalu, Andres and De Boer, Rudolf A. and Van Der Meer, Peter and Van Der Harst, Pim and Gambaro, Giovanni and Ingelsson, Erik and Lind, Lars and De Bakker, Paul I W and Numans, Mattijs E. and Brandslund, Ivan and Christensen, Cramer and Petersen, Eva R B and Korpi-Hyövälti, Eeva and Oksa, Heikki and Chambers, John C. and Kooner, Jaspal S. and Blakemore, Alexandra I F and Franks, Steve and Jarvelin, Marjo Riitta and Husemoen, Lise L. and Linneberg, Allan and Skaaby, Tea and Thuesen, Betina and Karpe, Fredrik and Tuomilehto, Jaakko and Doney, Alex S F and Morris, Andrew D. and Palmer, Colin N A and Holmen, Oddgeir Lingaas and Hveem, Kristian and Willer, Cristen J. and Tuomi, Tiinamaija and Groop, Leif and Käräjämäki, Annemari and Palotie, Aarno and Ripatti, Samuli and Salomaa, Veikko and Alam, Dewan S. and Majumder, Abdulla Al Shafi and Di Angelantonio, Emanuele and Chowdhury, Rajiv and McCarthy, Mark I. and Poulter, Neil and Stanton, Alice V. and Sever, Peter and Amouyel, Philippe and Arveiler, Dominique and Blankenberg, Stefan and Ferrières, Jean and Kee, Frank and Kuulasmaa, Kari and Müller-Nurasyid, Martina and Veronesi, Giovanni and Virtamo, Jarmo and Deloukas, Panos and Elliott, Paul and Zeggini, Eleftheria and Kathiresan, Sekar and Melander, Olle and Kuusisto, Johanna and Laakso, Markku and Padmanabhan, Sandosh and Porteous, David J. and Hayward, Caroline and Scotland, Generation and Collins, Francis S. and Mohlke, Karen L. and Hansen, Torben and Pedersen, Oluf and Boehnke, Michael and Stringham, Heather M. and Frossard, Philippe and Newton-Cheh, Christopher and Tobin, Martin D. and Nordestgaard, Børge Grønne and Caulfield, Mark J. and Mahajan, Anubha and Morris, Andrew P. and Tomaszewski, Maciej and Samani, Nilesh J. and Saleheen, Danish and Asselbergs, Folkert W. and Lindgren, Cecilia M. and Danesh, John and Wain, Louise V. and Butterworth, Adam S. and Howson, Joanna M M and Munroe, Patricia B.},
  issn         = {1061-4036},
  language     = {eng},
  month        = {10},
  number       = {10},
  pages        = {1151--1161},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension},
  url          = {http://dx.doi.org/10.1038/ng.3654},
  volume       = {48},
  year         = {2016},
}