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, Samuel, 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, De Craen, Anton J. M., Trompet, Stella, Luan, Jian’an, Scott, Robert A., Harris, Sarah E., Liewald, David C. M., Marioni, Riccardo, Menni, Cristina, Farmaki, Aliki-Eleni, Hallmans, Göran, Renstrom, Frida, Huffman, Jennifer E., Hassinen, Maija, Burgess, Stephen, Vasan, Ramachandran S., Felix, Janine F., Uria-Nickelsen, Maria, Malarstig, 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, Tõnu, Magi, Reedik, Metspalu, Andres, De Boer, Rudolf A., Van Der Meer, Peter, Van Der Harst, Pim, Gambaro, Giovanni, Ingelsson, Erik, Lind, Lars, De Bakker, Paul I. W., 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., Majumder, 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, Muller-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 H., 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. and Munroe, Patricia B. (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nature Genetics, 48 10: 1151-1161. doi:10.1038/ng.3654


Author 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
Samuel, 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
De Craen, Anton J. M.
Trompet, Stella
Luan, Jian’an
Scott, Robert A.
Harris, Sarah E.
Liewald, David C. M.
Marioni, Riccardo
Menni, Cristina
Farmaki, Aliki-Eleni
Hallmans, Göran
Renstrom, Frida
Huffman, Jennifer E.
Hassinen, Maija
Burgess, Stephen
Vasan, Ramachandran S.
Felix, Janine F.
Uria-Nickelsen, Maria
Malarstig, 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, Tõnu
Magi, Reedik
Metspalu, Andres
De Boer, Rudolf A.
Van Der Meer, Peter
Van Der Harst, Pim
Gambaro, Giovanni
Ingelsson, Erik
Lind, Lars
De Bakker, Paul I. W.
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.
Majumder, 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
Muller-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 H.
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.
Title Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1038/ng.3654
Open Access Status PMC
Volume 48
Issue 10
Start page 1151
End page 1161
Total pages 11
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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 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.
Formatted 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 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID RG/15/15/31742
G0700931
R01 DK072193
R01 HL127564
MR/L01341X/1
MR/K026992/1
G0601966
MC_UU_12015/1
CZD/16/6/4
MC_PC_U127561128
U01 DK062370
MR/K006584/1
RG/14/5/30893
R01 HD057194
G0600237
MC_UU_12013/5
P30 DK020595
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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