Large-scale association analysis identifies new risk loci for coronary artery disease

Panos Deloukas, Stavroula Kanoni, Christina Willenborg, Martin Farrall, Themistocles L. Assimes, John R. Thompson, Erik Ingelsson, Danish Saleheen, Jeanette Erdmann, Benjamin A. Goldstein, Kathleen Stirrups, Inke R. König, Jean Baptiste Cazier, Åsa Johansson, Alistair S. Hall, Jong Young Lee, Cristen J. Willer, John C. Chambers, Tõnu Esko, Lasse FolkersenAnuj Goel, Elin Grundberg, Aki S. Havulinna, Weang K. Ho, Jemma C. Hopewell, Niclas Eriksson, Marcus E. Kleber, Kati Kristiansson, Per Lundmark, Leo Pekka Lyytikäinen, Suzanne Rafelt, Dmitry Shungin, Rona J. Strawbridge, Gudmar Thorleifsson, Emmi Tikkanen, Natalie Van Zuydam, Benjamin F. Voight, Lindsay L. Waite, Weihua Zhang, Andreas Ziegler, Devin Absher, David Altshuler, Anthony J. Balmforth, Inês Barroso, Peter S. Braund, Christof Burgdorf, Simone Claudi-Boehm, David Cox, Maria Dimitriou, Ron Do, Alex S.F. Doney, Nour Eddine El Mokhtari, Per Eriksson, Krista Fischer, Pierre Fontanillas, Anders Franco-Cereceda, Bruna Gigante, Leif Groop, Stefan Gustafsson, Jörg Hager, Göran Hallmans, Bok Ghee Han, Sarah E. Hunt, Hyun M. Kang, Thomas Illig, Thorsten Kessler, Joshua W. Knowles, Genovefa Kolovou, Johanna Kuusisto, Claudia Langenberg, Cordelia Langford, Karin Leander, Marja Liisa Lokki, Anders Lundmark, Mark I. McCarthy, Christa Meisinger, Olle Melander, Evelin Mihailov, Seraya Maouche, Andrew D. Morris, Martina Müller-Nurasyid, Kjell Nikus, John F. Peden, N. William Rayner, Asif Rasheed, Silke Rosinger, Diana Rubin, Moritz P. Rumpf, Arne Schäfer, Mohan Sivananthan, Ci Song, Alexandre F.R. Stewart, Sian Tsung Tan, Gudmundur Thorgeirsson, C. Ellen Van Der Schoot, Peter J. Wagner, George A. Wells, Philipp S. Wild, Tsun Po Yang, Philippe Amouyel, Dominique Arveiler, Hanneke Basart, Michael Boehnke, Eric Boerwinkle, Paolo Brambilla, Francois Cambien, Adrienne L. Cupples, Ulf De Faire, Abbas Dehghan, Patrick Diemert, Stephen E. Epstein, Alun Evans, Marco M. Ferrario, Jean Ferrières, Dominique Gauguier, Alan S. Go, Alison H. Goodall, Villi Gudnason, Stanley L. Hazen, Hilma Holm, Carlos Iribarren, Yangsoo Jang, Mika Kähönen, Frank Kee, Hyo Soo Kim, Norman Klopp, Wolfgang Koenig, Wolfgang Kratzer, Kari Kuulasmaa, Markku Laakso, Reijo Laaksonen, Ji Young Lee, Lars Lind, Willem H. Ouwehand, Sarah Parish, Jeong E. Park, Nancy L. Pedersen, Annette Peters, Thomas Quertermous, Daniel J. Rader, Veikko Salomaa, Eric Schadt, Svati H. Shah, Juha Sinisalo, Klaus Stark, Kari Stefansson, David Alexandre Trégouët, Jarmo Virtamo, Lars Wallentin, Nicholas Wareham, Martina E. Zimmermann, Markku S. Nieminen, Christian Hengstenberg, Manjinder S. Sandhu, Tomi Pastinen, Ann Christine Syvänen, G. Kees Hovingh, George Dedoussis, Paul W. Franks, Terho Lehtimäki, Andres Metspalu, Pierre A. Zalloua, Agneta Siegbahn, Stefan Schreiber, Samuli Ripatti, Stefan S. Blankenberg, Markus Perola, Robert Clarke, Bernhard O. Boehm, Christopher O'Donnell, Muredach P. Reilly, Winfried März, Rory Collins, Sekar Kathiresan, Anders Hamsten, Jaspal S. Kooner, Unnur Thorsteinsdottir, John Danesh, Colin N.A. Palmer, Robert Roberts, Hugh Watkins, Heribert Schunkert, Nilesh J. Samani

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Abstract

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalNature Genetics
Volume45
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Deloukas, P., Kanoni, S., Willenborg, C., Farrall, M., Assimes, T. L., Thompson, J. R., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, B. A., Stirrups, K., König, I. R., Cazier, J. B., Johansson, Å., Hall, A. S., Lee, J. Y., Willer, C. J., Chambers, J. C., Esko, T., ... Samani, N. J. (2013). Large-scale association analysis identifies new risk loci for coronary artery disease. Nature Genetics, 45(1), 25-33. https://doi.org/10.1038/ng.2480