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

Deloukas, Panos ; Kanoni, Stavroula ; Willenborg, Christina ; Farrall, Martin ; Assimes, Themistocles L. ; Thompson, John R. ; Ingelsson, Erik ; Saleheen, Danish ; Erdmann, Jeanette and Goldstein, Benjamin A. , et al. (2013) In Nature Genetics 45(1). p.25-33
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
45
issue
1
pages
25 - 33
publisher
Nature Publishing Group
external identifiers
  • wos:000312838800009
  • scopus:84871969762
  • pmid:23202125
ISSN
1546-1718
DOI
10.1038/ng.2480
language
English
LU publication?
yes
id
a73cb026-921b-4b98-ae31-9ee47cfbda87 (old id 3481131)
date added to LUP
2016-04-01 13:44:24
date last changed
2024-01-09 16:45:10
@article{a73cb026-921b-4b98-ae31-9ee47cfbda87,
  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) &lt; 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.}},
  author       = {{Deloukas, Panos and Kanoni, Stavroula and Willenborg, Christina and Farrall, Martin and Assimes, Themistocles L. and Thompson, John R. and Ingelsson, Erik and Saleheen, Danish and Erdmann, Jeanette and Goldstein, Benjamin A. and Stirrups, Kathleen and Koenig, Inke R. and Cazier, Jean-Baptiste and Johansson, Asa and Hall, Alistair S. and Lee, Jong-Young and Willer, Cristen J. and Chambers, John C. and Esko, Tonu and Folkersen, Lasse and Goel, Anuj and Grundberg, Elin and Havulinna, Aki S. and Ho, Weang K. and Hopewell, Jemma C. and Eriksson, Niclas and Kleber, Marcus E. and Kristiansson, Kati and Lundmark, Per and Lyytikainen, Leo-Pekka and Rafelt, Suzanne and Shungin, Dmitry and Strawbridge, Rona J. and Thorleifsson, Gudmar and Tikkanen, Emmi and Van Zuydam, Natalie and Voight, Benjamin F. and Waite, Lindsay L. and Zhang, Weihua and Ziegler, Andreas and Absher, Devin and Altshuler, David and Balmforth, Anthony J. and Barroso, Ines and Braund, Peter S. and Burgdorf, Christof and Claudi-Boehm, Simone and Cox, David and Dimitriou, Maria and Do, Ron and Doney, Alex S. F. and El Mokhtari, NourEddine and Eriksson, Per and Fischer, Krista and Fontanillas, Pierre and Franco-Cereceda, Anders and Gigante, Bruna and Groop, Leif and Gustafsson, Stefan and Hager, Joerg and Hallmans, Goran and Han, Bok-Ghee and Hunt, Sarah E. and Kang, Hyun M. and Illig, Thomas and Kessler, Thorsten and Knowles, Joshua W. and Kolovou, Genovefa and Kuusisto, Johanna and Langenberg, Claudia and Langford, Cordelia and Leander, Karin and Lokki, Marja-Liisa and Lundmark, Anders and McCarthy, Mark I. and Meisinger, Christa and Melander, Olle and Mihailov, Evelin and Maouche, Seraya and Morris, Andrew D. and Mueller-Nurasyid, Martina and Nikus, Kjell and Peden, John F. and Rayner, N. William and Rasheed, Asif and Rosinger, Silke and Rubin, Diana and Rumpf, Moritz P. and Schaefer, Arne and Sivananthan, Mohan and Song, Ci and Stewart, Alexandre F. R. and Tan, Sian-Tsung and Thorgeirsson, Gudmundur and van der Schoot, C. Ellen and Wagner, Peter J. and Wells, George A. and Wild, Philipp S. and Yang, Tsun-Po and Amouyel, Philippe and Arveiler, Dominique and Basart, Hanneke and Boehnke, Michael and Boerwinkle, Eric and Brambilla, Paolo and Cambien, Francois and Cupples, Adrienne L. and de Faire, Ulf and Dehghan, Abbas and Diemert, Patrick and Epstein, Stephen E. and Evans, Alun and Ferrario, Marco M. and Ferrieres, Jean and Gauguier, Dominique and Go, Alan S. and Goodall, Alison H. and Gudnason, Villi and Hazen, Stanley L. and Holm, Hilma and Iribarren, Carlos and Jang, Yangsoo and Kahonen, Mika and Kee, Frank and Kim, Hyo-Soo and Klopp, Norman and Koenig, Wolfgang and Kratzer, Wolfgang and Kuulasmaa, Kari and Laakso, Markku and Laaksonen, Reijo and Lee, Ji-Young and Lind, Lars and Ouwehand, Willem H. and Parish, Sarah and Park, Jeong E. and Pedersen, Nancy L. and Peters, Annette and Quertermous, Thomas and Rader, Daniel J. and Salomaa, Veikko and Schadt, Eric and Shah, Svati H. and Sinisalo, Juha and Stark, Klaus and Stefansson, Kari and Tregouet, David-Alexandre and Virtamo, Jarmo and Wallentin, Lars and Wareham, Nicholas and Zimmermann, Martina E. and Nieminen, Markku S. and Hengstenberg, Christian and Sandhu, Manjinder S. and Pastinen, Tomi and Syvanen, Ann-Christine and Hovingh, G. Kees and Dedoussis, George and Franks, Paul and Lehtimaki, Terho and Metspalu, Andres and Zalloua, Pierre A. and Siegbahn, Agneta and Schreiber, Stefan and Ripatti, Samuli and Blankenberg, Stefan S. and Perola, Markus and Clarke, Robert and Boehm, Bernhard O. and O'Donnell, Christopher and Reilly, Muredach P. and Maerz, Winfried and Collins, Rory and Kathiresan, Sekar and Hamsten, Anders and Kooner, Jaspal S. and Thorsteinsdottir, Unnur and Danesh, John and Palmer, Colin N. A. and Roberts, Robert and Watkins, Hugh and Schunkert, Heribert and Samani, Nilesh J.}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{25--33}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Large-scale association analysis identifies new risk loci for coronary artery disease}},
  url          = {{http://dx.doi.org/10.1038/ng.2480}},
  doi          = {{10.1038/ng.2480}},
  volume       = {{45}},
  year         = {{2013}},
}