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

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

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

https://hdl.handle.net/10779/lincoln.26372275

journal contribution

posted on 2024-07-25, 15:48 authored by P. Surendran, F. Drenos, R. Young, H. Warren, J.P. Cook, A.K. Manning, N. Grarup, X. Sim, D.R. Barnes, K. Witkowska, J.R. Staley, V. Tragante, T. Tukiainen, Hanieh Yaghootkar, N. Masca, D.F. Freitag, T. Ferreira, O. Giannakopoulou, A. Tinker, M. Harakalova, E. Mihailov, C. Liu, A.T. Kraja, S.F. Nielsen, A. Rasheed, M. Samuel, W. Zhao, L.L. Bonnycastle, A.U. Jackson, N. Narisu, A.J. Swift, L. Southam, J. Marten, J.R. Huyghe, A. Stančáková, C. Fava, T. Ohlsson, A. Matchan, K.E. Stirrups, J. Bork-Jensen, A.P. Gjesing, J. Kontto, M. Perola, S. Shaw-Hawkins, A.S. Havulinna, H. Zhang, L.A. Donnelly, C.J. Groves, N.W. Rayner, M.J. Neville, N.R. Robertson, A.M. Yiorkas, K.-H. Herzig, E. Kajantie, W. Zhang, S.M. Willems, L. Lannfelt, G. Malerba, N. Soranzo, E. Trabetti, N. Verweij, E. Evangelou, A. Moayyeri, A.-C. Vergnaud, C.P. Nelson, A. Poveda, T.V. Varga, M. Caslake, A.J.M. De, S. Trompet, J. Luan, R.A. Scott, S.E. Harris, D.C.M. Liewald, R. Marioni, C. Menni, A.-E. Farmaki, G. Hallmans, F. Renström, J.E. Huffman, M. Hassinen, S. Burgess, R.S. Vasan, J.F. Felix, M. Uria-Nickelsen, A. Malarstig, D.F. Reilly, M. Hoek, T.F. Vogt, H. Lin, W. Lieb, M. Traylor, H.S. Markus, H.M. Highland, A.E. Justice, E. Marouli, J. Lindström, M. Uusitupa, P. Komulainen, T.A. Lakka, R. Rauramaa, O. Polasek, I. Rudan, O. Rolandsson, P.W. Franks, G. Dedoussis, T.D. Spector, P. Jousilahti, S. Männistö, I.J. Deary, J.M. Starr, C. Langenberg, N.J. Wareham, M.J. Brown, A.F. Dominiczak, J.M. Connell, J.W. Jukema, N. Sattar, I. Ford, C.J. Packard, T. Esko, R. Mägi, A. Metspalu, R.A. De, P. Van, G. Gambaro, E. Ingelsson, L. Lind, P.I.W. De, M.E. Numans, I. Brandslund, C. Christensen, E.R.B. Petersen, E. Korpi-Hyövälti, H. Oksa, J.C. Chambers, J.S. Kooner, A.I.F. Blakemore, S. Franks, M.-R. Jarvelin, L.L. Husemoen, A. Linneberg, T. Skaaby, B. Thuesen, F. Karpe, J. Tuomilehto, A.S.F. Doney, A.D. Morris, C.N.A. Palmer, O.L. Holmen, K. Hveem, C.J. Willer, T. Tuomi, L. Groop, A. Käräjämäki, A. Palotie, S. Ripatti, V. Salomaa, D.S. Alam, A.A.S. Majumder, E. Di, R. Chowdhury, M.I. McCarthy, N. Poulter, A.V. Stanton, P. Sever, P. Amouyel, D. Arveiler, S. Blankenberg, J. Ferrières, F. Kee, K. Kuulasmaa, M. Müller-Nurasyid, G. Veronesi, J. Virtamo, P. Deloukas, P. Elliott, E. Zeggini, S. Kathiresan, O. Melander, J. Kuusisto, M. Laakso, S. Padmanabhan, D.J. Porteous, C. Hayward, G. Scotland, F.S. Collins, K.L. Mohlke, T. Hansen, O. Pedersen, M. Boehnke, H.M. Stringham, P. Frossard, C. Newton-Cheh, M.D. Tobin, Bø.G. Nordestgaard, M.J. Caulfield, A. Mahajan, A.P. Morris, M. Tomaszewski, N.J. Samani, D. Saleheen, F.W. Asselbergs, C.M. Lindgren, J. Danesh, L.V. Wain, A.S. Butterworth, J.M.M. Howson, P.B. Munroe

<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 (>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. © 2016 Nature America, Inc. All rights reserved.</p>

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Publication Title

Nature Genetics

Volume

48

Issue

10

Pages/Article Number

1151-1161

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Nature Publishing Group

External DOI

https://www.doi.org/10.1038/ng.3654

ISSN

10614036

Date Accepted

2016-08-02

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

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