Genome-wide association study identifies eight loci associated with blood pressure

Christopher Newton-Cheh, Toby Johnson, Vesela Gateva, Martin D. Tobin, Murielle Bochud, Lachlan Coin, Samer S. Najjar, Jing Hua Zhao, Simon C. Heath, Susana Eyheramendy, Konstantinos Papadakis, Benjamin F. Voight, Laura J. Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C. Chambers, Kay Tee Khaw, Peter NilssonPim Van Der Harst, Silvia Polidoro, Diederick E. Grobbee, N. Charlotte Onland-Moret, Michiel L. Bots, Louise V. Wain, Katherine S. Elliott, Alexander Teumer, Jian'An Luan, Gavin Lucas, Johanna Kuusisto, Paul R. Burton, David Hadley, Wendy L. McArdle, Morris Brown, Anna Dominiczak, Stephen J. Newhouse, Nilesh J. Samani, John Webster, Eleftheria Zeggini, Jacques S. Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Peter Vollenweider, Gerard Waeber, Dawn M. Waterworth, Xin Yuan, Leif Groop, Marju Orho-Melander, Alessandra Allione, Alessandra Di Gregorio, Simonetta Guarrera, Salvatore Panico, Fulvio Ricceri, Valeria Romanazzi, Carlotta Sacerdote, Paolo Vineis, Inês Barroso, Manjinder S. Sandhu, Robert N. Luben, Gabriel J. Crawford, Pekka Jousilahti, Markus Perola, Michael Boehnke, Lori L. Bonnycastle, Francis S. Collins, Anne U. Jackson, Karen L. Mohlke, Heather M. Stringham, Timo T. Valle, Cristen J. Willer, Richard N. Bergman, Mario A. Morken, Angela Döring, Christian Gieger, Thomas Illig, Thomas Meitinger, Elin Org, Arne Pfeufer, H. Erich Wichmann, Sekar Kathiresan, Jaume Marrugat, Christopher J. O'Donnell, Stephen M. Schwartz, David S. Siscovick, Isaac Subirana, Nelson B. Freimer, Anna Liisa Hartikainen, Mark I. McCarthy, Paul F. O'Reilly, Leena Peltonen, Anneli Pouta, Paul E. De Jong, Harold Snieder, Wiek H. Van Gilst, Robert Clarke, Anuj Goel, Anders Hamsten, David Altshuler, Marjo Ritta Jarvelin, Paul Elliott, Edward G. Lakatta, Nita Forouhi, Nicholas J. Wareham, Ruth J.F. Loos, Panos Deloukas, Sheila A. Bingham, Diana Zelenika, David P. Strachan, Nicole Soranzo, Frances M. Williams, Guangju Zhai, Tim D. Spector, John F. Peden, Hugh Watkins, Luigi Ferrucci, Mark Caulfield, Patricia B. Munroe, Göran Berglund, Olle Melander, Guiseppe Matullo, Cuno S. Uiterwaal, Yvonne T. van der Schouw, Mattijs E. Numans, Florian Ernst, Georg Homuth, Uwe Völker, Roberto Eluosa, Markku Laakso, John M. Connell, Vincent Mooser, Veikko Salomaa, Jaakko Tuomilehto, Maris Laan, Gerjan Navis, Udo Seedorf, Ann Christine Syvänen, Giovanni Tognoni, Serena Sanna, Manuela Uda, Paul Scheet, David Schlessinger, Angelo Scuteri, Marcus Dörr, Stephan B. Felix, Thorsten Reffelmann, Roberto Lorbeer, Henry Völzke, Rainer Rettig, Pilar Galan, Serge Hercberg, Sheila A. Bingham, Jaspal S. Kooner, Stefania Bandinelli, Pierre Meneton, Gonçalo Abecasis, John R. Thompson, Carolina A. Braga Marcano, Beverley Barke, Richard Dobson, Johannie Gungadoo, Kate L. Lee, Abiodun Onipinla, I. Wallace, Mingzhan Xue, David G. Clayton, Hin Tak Leung, Sarah Nutland, Neil M. Walker, John A. Todd, Helen E. Stevens, David B. Dunger, Barry Widmer, Kate Downes, Lou R. Cardon, Dominic P. Kwiatkowski, Jeffrey C. Barrett, David Evans, Andrew P. Morris, Cecilia M. Lindgren, Nigel W. Rayner, Nicolas Timpson, Emily Lyons, Fredrik Vannberg, Adrian V.S. Hill, Yik Ying Teo, Kirk A. Rockett, Nick Craddock, Antony P. Attwood, Claire Bryan, Suzannah J. Bumpstead, Amy Chaney, Jilur Ghori, Rhian G. William, Sarah E. Hunt, Michael Inouye, Emma Keniry, Emma King, Ralph McGinnis, Simon Potter, Rathi Ravindrarajan, Pamela Whittaker, David Withers, David Bentley, Christopher J. Groves, Audrey Duncanson, Willem H. Ouwehand, James P. Boorman, Barbera Cant, Jennifer D. Jolley, Alexandra S. Knight, Kerstin Koch, Niall C. Taylor, Nicholas A. Watkins, Thilo Winzer, Peter S. Braund, Richard J. Dixon, Massimo Mangino, Suzanne Stevens, Peter Donnely, Dan Davidson, Jonathan L. Marchini, I. C.A. Spencer, Niall J. Cardin, Teresa Ferreira, Joanne Pereira-Gale, Ingeleif B. Hallgrimsdottir, Bryan N. Howie, Zhan Su, Damjan Vukcevic, Doug Easton, Ursula Everson, Judith M. Hussey, Elizabeth Meech, Christopher V. Prowse, Graham R. Walters, Richard W. Jones, Susan M. Ring, Marcus Prembey, Gerome Breen, David St. Clair, Sian Ceasar, Katherine Gordon-Smith, Lisa Jones, Elaine K. Green, Detelinea Grozeva, Marian L. Hamshere, Peter A. Holmans, Ian R. Jones, George Kirov, Valentina Moskovina, Ivan Nikolov, Michael C. O'Donovan, Michael J. Owen, Nick Craddock, David A. Collier, Amanda Elkin, Anne Farmer, Richard Williamson, Peter McGruffin, Allan H. Young, I. Nicol Ferrier, Stephen G. Ball, Anthony J. Balmforth, Jennifer H. Barrett, D. Timothy Bishop, Mark M. Iles, Azhar Maqbool, Nadira Yuldasheva, Alistair S. Hall, Francesca Bredin, Mark Tremelling, Miles Parkes, Hazel Drummond, Charles W. Lees, Elaine R. Nimmo, Jack Satsangi, Sheila A. Fisher, Cathryn M. Lewis, Clive M. Onnie, Nathalie J. Prescott, Christopher G. Mathew, Alastair Forbes, Jeremy Sanderson, Christopher Mathew, Jamie Barbour, M. Khalid Mohiuddin, Catherine E. Todhunter, John C. Mansfield, Tariq Ahmad, Fraser R. Cummings, Derek P. Jewell, Anne Barton, Ian N. Bruce, Hannah Donovan, Steve Eyre, Paul D. Gilbert, Samantha L. Hider, Anne M. Hinks, Sally L. John, Catherine Potter, Alan J. Silman, Deborah P.M. Symmons, Wendy Thomson, Jane Worthington, Timothy M. Frayling, Rachel M. Freathy, Hana Lango, John R.B. Perry, Michael N. Weedon, Andrew T. Hattersley, Beverley M. Shields, Graham A. Hitman, Mark Walker, Melanie Newport, Giorgio Sirugo, David Conway, Muminatou Jallow, Linda A. Bradbury, Jennifer L. Pointon, Matthew A. Brown, Claire Farrar, Paul Wordsworth, Jayne A. Franklyn, Joanne M. Heward, Matthew J. Simmonds, Stephen C.L. Cough, Sheila Seal, Michael R. Stratton, Nazneen Rahman, An Goris, Stephen J. Sawcer, Alastair Compston

Research output: Contribution to journalArticle

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)666-676
Number of pages11
JournalNature genetics
Volume41
Issue number6
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Genetics

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    Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M. D., Bochud, M., Coin, L., Najjar, S. S., Zhao, J. H., Heath, S. C., Eyheramendy, S., Papadakis, K., Voight, B. F., Scott, L. J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J. C., Khaw, K. T., ... Compston, A. (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nature genetics, 41(6), 666-676. https://doi.org/10.1038/ng.361