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.; Witkowska, Kate; Staley, James R.; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F.; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T.; Nielsen, Sune Fallgaard; Rasheed, Asif; Samue, Maria; Zhao, Wei; Bonnycastle, Lori L.; Jackson, Anne U.; Narisu, Narisu; Swift, Amy J.; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R.; Stancakova, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E.; Bork-Jensen, Jette; Gjesing, Anette P.; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S.; Zhang, He; Donnelly, Louise A.; Groves, Christopher J.; Rayner, N. William; Neville, Matt J.; Robertson, Neil R.; Yiorkas, Andrianos M.; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M.; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P.; Poveda, Alaitz; Varga, Tibor V.; Caslake, Muriel; Craen, Anton J. M. de; Trompet, Stella; Luan, Jian'an; Scott, Robert A.; Harris, Sarah E.; Liewald, David C. M.; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Goran; Renstrom, Frida; Huffman, Jennifer E.; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S.; Felix, Janine F.; Uria-Nickelsen, Maria; Malarstign, Anders; Reilly, Dermot F.; Hoek, Maarten; Vogt, Thomas F.; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S.; Highland, Heather M.; Justice, Anne E.; Marouli, Eirini; Lindstrom, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A.; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W.; Dedoussis, George; Spector, Timothy D.; Jousilahti, Pekka; Mannisto, Satu; Deary, Ian J.; Starr, John M.; Langenberg, Claudia; Wareham, Nick J.; Brown, Morris J.; Dominiczak, Anna F.; Connell, John M.; Jukema, J. Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J.; Esko, Tonu; Magi, Reedik; Metspalu, Andres; de Boer, Rudolf A.; Meer, Peter van der; Harst, Pim van der; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; Bakker, Paul I. W. de; Numans, Mattijs E.; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R. B.; Korpi-Hyovalti, Eeva; Oksa, Heikki; Chambers, John C.; Kooner, Jaspal S.; Blakemore, Alexandra I. F.; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L.; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J.; Tuomi, Tiinamaija; Groop, Leif; Karajamaki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S.; Majmnder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I.; Poulter, Neil; Stanton, Alice V.; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrieres, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J.; Hayward, Caroline; Scotland, Generation; Collins, Francis S.; Mohlke, Karen L.; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M.; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D.; Nordestgaard, Borge Gronne; Caulfield, Mark J.; Mahajan, Anubha; Morris, Andrew P.; Tomaszewski, Maciej; Samani, Nilesh J.; Saleheen, Danish; Asselbergs, Folkert W.; Lindgren, Cecilia M.; Danesh, John; Wain, Louise V.; Butterworth, Adam S.; Howson, Joanna M. M.; Munroe, Patricia B. (2016): Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. In: Nature Genetics, Vol. 48, No. 10: pp. 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 similar to 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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1061-4036
• Language: English