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

Publication

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

Journal Paper/Review - Sep 12, 2016

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

Citation

Palotie A, Linneberg A, Husemoen L, Jarvelin M, Franks S, Blakemore A, Kooner J, Chambers J, Oksa H, Korpi-Hyövälti E, Petersen E, Christensen C, Skaaby T, Thuesen B, Käräjämäki A, Groop L, Tuomi T, Willer C, Hveem K, Holmen O, Palmer C, Morris A, Doney A, Tuomilehto J, Karpe F, Brandslund I, Numans M, Jukema J, Connell J, Dominiczak A, Brown M, Wareham N, Langenberg C, Starr J, Deary I, Männistö S, Jousilahti P, Spector T, Sattar N, Ford I, de Bakker P, Lind L, Ingelsson E, Gambaro G, van der Harst P, van der Meer P, de Boer R, Metspalu A, Mägi R, Esko T, Packard C, Dedoussis G, Ripatti S, Munroe P, Tobin M, Newton-Cheh C, Frossard P, Stringham H, Boehnke M, Pedersen O, Hansen T, Mohlke K, Collins F, Scotland G, Hayward C, Nordestgaard B, Caulfield M, Howson J, Butterworth A, Wain L, Danesh J, Lindgren C, Asselbergs F, Saleheen D, Samani N, Tomaszewski M, Morris A, Mahajan A, Porteous D, Padmanabhan S, Blankenberg S, Arveiler D, Amouyel P, Sever P, Stanton A, Poulter N, McCarthy M, Chowdhury R, Di Angelantonio E, Shafi Majumder A, Alam D, Ferrieres J, Kee F, Laakso M, Kuusisto J, Melander O, Kathiresan S, Zeggini E, Elliott P, Deloukas P, Virtamo J, Veronesi G, Müller-Nurasyid M, Kuulasmaa K, Salomaa V, Franks P, Yiorkas A, Matchan A, Ohlsson T, Fava C, Stančáková A, Huyghe J, Marten J, Southam L, Swift A, Narisu N, Jackson A, Bonnycastle L, Stirrups K, Bork-Jensen J, Robertson N, Neville M, Rayner N, Groves C, Donnelly L, Zhang H, Havulinna A, Shaw-Hawkins S, Perola M, Kontto J, Gjesing A, Zhao W, Samuel M, Tragante V, Staley J, Witkowska K, Barnes D, Sim X, Grarup N, Manning A, Cook J, Warren H, Young R, Drenos F, Tukiainen T, Yaghootkar H, Rasheed A, Fallgaard Nielsen S, Kraja A, Liu C, Mihailov E, Harakalova M, Tinker A, Giannakopoulou O, Ferreira T, Freitag D, Masca N, Surendran P, Herzig K, Rolandsson O, Lin H, Vogt T, Hoek M, Reily D, Malarstig A, Uria-Nickelsen M, Felix J, Vasan R, Burgess S, Hassinen M, Lieb W, Traylor M, Rudan I, Polasek O, Rauramaa R, Lakka T, Komulainen P, Uusitupa M, Lindström J, Marouli E, Justice A, Highland H, Markus H, Huffman J, Renström F, Nelson C, Vergnaud A, Moayyeri A, Evangelou E, Verweij N, Trabetti E, Soranzo N, Malerba G, Lannfelt L, Willems S, Zhang W, Poveda A, Varga T, Hallmans G, Farmaki A, Menni C, Marioni R, Liewald D, Harris S, Scott R, Luan J, Trompet S, de Craen A, Caslake M, Kajantie E. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat Genet 2016; 48:1151-1161.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2016; 48

Publication Date

Sep 12, 2016

Issn Electronic

1546-1718

Pages

1151-1161

Brief description/objective

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.