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 language | English |
|---|---|
| Pages (from-to) | 25-33 |
| Number of pages | 9 |
| Journal | Nature Genetics |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Jan |
All Science Journal Classification (ASJC) codes
- Genetics
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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; Goldstein, Benjamin A.; Stirrups, Kathleen; König, Inke R.; Cazier, Jean Baptiste; Johansson, Åsa; Hall, Alistair S.; Lee, Jong Young; Willer, Cristen J.; Chambers, John C.; Esko, Tõnu; Folkersen, Lasse; Goel, Anuj; Grundberg, Elin; Havulinna, Aki S.; Ho, Weang K.; Hopewell, Jemma C.; Eriksson, Niclas; Kleber, Marcus E.; Kristiansson, Kati; Lundmark, Per; Lyytikäinen, Leo Pekka; Rafelt, Suzanne; Shungin, Dmitry; Strawbridge, Rona J.; Thorleifsson, Gudmar; Tikkanen, Emmi; Van Zuydam, Natalie; Voight, Benjamin F.; Waite, Lindsay L.; Zhang, Weihua; Ziegler, Andreas; Absher, Devin; Altshuler, David; Balmforth, Anthony J.; Barroso, Inês; Braund, Peter S.; Burgdorf, Christof; Claudi-Boehm, Simone; Cox, David; Dimitriou, Maria; Do, Ron; Doney, Alex S.F.; El Mokhtari, Nour Eddine; Eriksson, Per; Fischer, Krista; Fontanillas, Pierre; Franco-Cereceda, Anders; Gigante, Bruna; Groop, Leif; Gustafsson, Stefan; Hager, Jörg; Hallmans, Göran; Han, Bok Ghee; Hunt, Sarah E.; Kang, Hyun M.; Illig, Thomas; Kessler, Thorsten; Knowles, Joshua W.; Kolovou, Genovefa; Kuusisto, Johanna; Langenberg, Claudia; Langford, Cordelia; Leander, Karin; Lokki, Marja Liisa; Lundmark, Anders; McCarthy, Mark I.; Meisinger, Christa; Melander, Olle; Mihailov, Evelin; Maouche, Seraya; Morris, Andrew D.; Müller-Nurasyid, Martina; Nikus, Kjell; Peden, John F.; Rayner, N. William; Rasheed, Asif; Rosinger, Silke; Rubin, Diana; Rumpf, Moritz P.; Schäfer, Arne; Sivananthan, Mohan; Song, Ci; Stewart, Alexandre F.R.; Tan, Sian Tsung; Thorgeirsson, Gudmundur; Van Der Schoot, C. Ellen; Wagner, Peter J.; Wells, George A.; Wild, Philipp S.; Yang, Tsun Po; Amouyel, Philippe; Arveiler, Dominique; Basart, Hanneke; Boehnke, Michael; Boerwinkle, Eric; Brambilla, Paolo; Cambien, Francois; Cupples, Adrienne L.; De Faire, Ulf; Dehghan, Abbas; Diemert, Patrick; Epstein, Stephen E.; Evans, Alun; Ferrario, Marco M.; Ferrières, Jean; Gauguier, Dominique; Go, Alan S.; Goodall, Alison H.; Gudnason, Villi; Hazen, Stanley L.; Holm, Hilma; Iribarren, Carlos; Jang, Yangsoo; Kähönen, Mika; Kee, Frank; Kim, Hyo Soo; Klopp, Norman; Koenig, Wolfgang; Kratzer, Wolfgang; Kuulasmaa, Kari; Laakso, Markku; Laaksonen, Reijo; Lee, Ji Young; Lind, Lars; Ouwehand, Willem H.; Parish, Sarah; Park, Jeong E.; Pedersen, Nancy L.; Peters, Annette; Quertermous, Thomas; Rader, Daniel J.; Salomaa, Veikko; Schadt, Eric; Shah, Svati H.; Sinisalo, Juha; Stark, Klaus; Stefansson, Kari; Trégouët, David Alexandre; Virtamo, Jarmo; Wallentin, Lars; Wareham, Nicholas; Zimmermann, Martina E.; Nieminen, Markku S.; Hengstenberg, Christian; Sandhu, Manjinder S.; Pastinen, Tomi; Syvänen, Ann Christine; Hovingh, G. Kees; Dedoussis, George; Franks, Paul W.; Lehtimäki, Terho; Metspalu, Andres; Zalloua, Pierre A.; Siegbahn, Agneta; Schreiber, Stefan; Ripatti, Samuli; Blankenberg, Stefan S.; Perola, Markus; Clarke, Robert; Boehm, Bernhard O.; O'Donnell, Christopher; Reilly, Muredach P.; März, Winfried; Collins, Rory; Kathiresan, Sekar; Hamsten, Anders; Kooner, Jaspal S.; Thorsteinsdottir, Unnur; Danesh, John; Palmer, Colin N.A.; Roberts, Robert; Watkins, Hugh; Schunkert, Heribert; Samani, Nilesh J.
In: Nature Genetics, Vol. 45, No. 1, 01.2013, p. 25-33.Research output: Contribution to journal › Article
TY - JOUR
T1 - Large-scale association analysis identifies new risk loci for coronary artery disease
AU - Deloukas, Panos
AU - Kanoni, Stavroula
AU - Willenborg, Christina
AU - Farrall, Martin
AU - Assimes, Themistocles L.
AU - Thompson, John R.
AU - Ingelsson, Erik
AU - Saleheen, Danish
AU - Erdmann, Jeanette
AU - Goldstein, Benjamin A.
AU - Stirrups, Kathleen
AU - König, Inke R.
AU - Cazier, Jean Baptiste
AU - Johansson, Åsa
AU - Hall, Alistair S.
AU - Lee, Jong Young
AU - Willer, Cristen J.
AU - Chambers, John C.
AU - Esko, Tõnu
AU - Folkersen, Lasse
AU - Goel, Anuj
AU - Grundberg, Elin
AU - Havulinna, Aki S.
AU - Ho, Weang K.
AU - Hopewell, Jemma C.
AU - Eriksson, Niclas
AU - Kleber, Marcus E.
AU - Kristiansson, Kati
AU - Lundmark, Per
AU - Lyytikäinen, Leo Pekka
AU - Rafelt, Suzanne
AU - Shungin, Dmitry
AU - Strawbridge, Rona J.
AU - Thorleifsson, Gudmar
AU - Tikkanen, Emmi
AU - Van Zuydam, Natalie
AU - Voight, Benjamin F.
AU - Waite, Lindsay L.
AU - Zhang, Weihua
AU - Ziegler, Andreas
AU - Absher, Devin
AU - Altshuler, David
AU - Balmforth, Anthony J.
AU - Barroso, Inês
AU - Braund, Peter S.
AU - Burgdorf, Christof
AU - Claudi-Boehm, Simone
AU - Cox, David
AU - Dimitriou, Maria
AU - Do, Ron
AU - Doney, Alex S.F.
AU - El Mokhtari, Nour Eddine
AU - Eriksson, Per
AU - Fischer, Krista
AU - Fontanillas, Pierre
AU - Franco-Cereceda, Anders
AU - Gigante, Bruna
AU - Groop, Leif
AU - Gustafsson, Stefan
AU - Hager, Jörg
AU - Hallmans, Göran
AU - Han, Bok Ghee
AU - Hunt, Sarah E.
AU - Kang, Hyun M.
AU - Illig, Thomas
AU - Kessler, Thorsten
AU - Knowles, Joshua W.
AU - Kolovou, Genovefa
AU - Kuusisto, Johanna
AU - Langenberg, Claudia
AU - Langford, Cordelia
AU - Leander, Karin
AU - Lokki, Marja Liisa
AU - Lundmark, Anders
AU - McCarthy, Mark I.
AU - Meisinger, Christa
AU - Melander, Olle
AU - Mihailov, Evelin
AU - Maouche, Seraya
AU - Morris, Andrew D.
AU - Müller-Nurasyid, Martina
AU - Nikus, Kjell
AU - Peden, John F.
AU - Rayner, N. William
AU - Rasheed, Asif
AU - Rosinger, Silke
AU - Rubin, Diana
AU - Rumpf, Moritz P.
AU - Schäfer, Arne
AU - Sivananthan, Mohan
AU - Song, Ci
AU - Stewart, Alexandre F.R.
AU - Tan, Sian Tsung
AU - Thorgeirsson, Gudmundur
AU - Van Der Schoot, C. Ellen
AU - Wagner, Peter J.
AU - Wells, George A.
AU - Wild, Philipp S.
AU - Yang, Tsun Po
AU - Amouyel, Philippe
AU - Arveiler, Dominique
AU - Basart, Hanneke
AU - Boehnke, Michael
AU - Boerwinkle, Eric
AU - Brambilla, Paolo
AU - Cambien, Francois
AU - Cupples, Adrienne L.
AU - De Faire, Ulf
AU - Dehghan, Abbas
AU - Diemert, Patrick
AU - Epstein, Stephen E.
AU - Evans, Alun
AU - Ferrario, Marco M.
AU - Ferrières, Jean
AU - Gauguier, Dominique
AU - Go, Alan S.
AU - Goodall, Alison H.
AU - Gudnason, Villi
AU - Hazen, Stanley L.
AU - Holm, Hilma
AU - Iribarren, Carlos
AU - Jang, Yangsoo
AU - Kähönen, Mika
AU - Kee, Frank
AU - Kim, Hyo Soo
AU - Klopp, Norman
AU - Koenig, Wolfgang
AU - Kratzer, Wolfgang
AU - Kuulasmaa, Kari
AU - Laakso, Markku
AU - Laaksonen, Reijo
AU - Lee, Ji Young
AU - Lind, Lars
AU - Ouwehand, Willem H.
AU - Parish, Sarah
AU - Park, Jeong E.
AU - Pedersen, Nancy L.
AU - Peters, Annette
AU - Quertermous, Thomas
AU - Rader, Daniel J.
AU - Salomaa, Veikko
AU - Schadt, Eric
AU - Shah, Svati H.
AU - Sinisalo, Juha
AU - Stark, Klaus
AU - Stefansson, Kari
AU - Trégouët, David Alexandre
AU - Virtamo, Jarmo
AU - Wallentin, Lars
AU - Wareham, Nicholas
AU - Zimmermann, Martina E.
AU - Nieminen, Markku S.
AU - Hengstenberg, Christian
AU - Sandhu, Manjinder S.
AU - Pastinen, Tomi
AU - Syvänen, Ann Christine
AU - Hovingh, G. Kees
AU - Dedoussis, George
AU - Franks, Paul W.
AU - Lehtimäki, Terho
AU - Metspalu, Andres
AU - Zalloua, Pierre A.
AU - Siegbahn, Agneta
AU - Schreiber, Stefan
AU - Ripatti, Samuli
AU - Blankenberg, Stefan S.
AU - Perola, Markus
AU - Clarke, Robert
AU - Boehm, Bernhard O.
AU - O'Donnell, Christopher
AU - Reilly, Muredach P.
AU - März, Winfried
AU - Collins, Rory
AU - Kathiresan, Sekar
AU - Hamsten, Anders
AU - Kooner, Jaspal S.
AU - Thorsteinsdottir, Unnur
AU - Danesh, John
AU - Palmer, Colin N.A.
AU - Roberts, Robert
AU - Watkins, Hugh
AU - Schunkert, Heribert
AU - Samani, Nilesh J.
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871969762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871969762&partnerID=8YFLogxK
U2 - 10.1038/ng.2480
DO - 10.1038/ng.2480
M3 - Article
C2 - 23202125
AN - SCOPUS:84871969762
VL - 45
SP - 25
EP - 33
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -