A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD), a modest number considering the apparent heritability of CAD. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ∼575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10−8 in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.

Mark I. McCarthy | Philippe Froguel | Paul Elliott | Nicole Soranzo | Gonçalo R. Abecasis | Peter Donnelly | Robert Clarke | Mohammad Ishaq | Simon C. Heath | Panos Deloukas | Leena Peltonen | Per Eriksson | Gunnar Olsson | John F. Peden | Martin Farrall | Hugh Watkins | Anuj Goel | H Ongen | Anna Helgadottir | Shapour Jalilzadeh | Theodosios Kyriakou | Peter Sleight | Jemma C. Hopewell | Rory Collins | Sarah Parish | A Offer | Louise Bowman | Jane Armitage | Richard Peto | Pamela Linksted | D Bennett | Danish Saleheen | A Rasheed | Moazzam Zaidi | Nabi Shah | Maria Samuel | Philippe M. Frossard | J Danesh | John C. Chambers | Weihua Zhang | Jaspal S. Kooner | Jörg Hager | Mark Lathrop | Marc Delepine | Kathy Stirrups | Muhammed Murtaza | Anders Hamsten | Rona J. Strawbridge | A Malarstig | John Öhrvik | Lasse Folkersen | Angela Silveira | Van 'T Hooft Fm | James Scott | J Sehmi | Simon C. Potter | Sarah E. Hunt | R. Gwilliam | S. J. Bumpstead | Elizabeth E. Gray | Sarah Edkins | Tomas Axelsson | A-C Syvanen | Anders Franco-Cereceda | Anders Gabrielsen | Udo Seedorf | S Rust | Gerd Assmann | Naveeduddin Ahmed | Angad S. Kooner | Mark J. Caulfield | Nilesh J. Samani | M-L Hellánius | Simona Barlera | Gianni Tognoni | MariaGrazia Franzosi | S. Pietri | F. Gori | F Green | Nadeem Hayyat Mallick | Muhammad Azhar | Khan Shah Zaman | Abdus Samad | Ali Raza Gardezi | F-U-R Memon | Tim D. Spector | Nieminen | Juha Sinisalo | Salomaa | Samuli Ripatti | Karin Leander | Bruna Gigante | U deFaire | Roberto Marchioli | Suthesh Sivapalaratnam | Jjp Kastelein | Trip | Eirini V. Theodoraki | George Dedoussis | Jc Engert | Salim Yusuf | Sonia S. Anand | P. Donnelly | P. Elliott | J. Danesh | R. Collins | T. Spector | M. McCarthy | P. Deloukas | G. Abecasis | K. Stirrups | L. Peltonen | S. Hunt | S. Heath | N. Samani | M. Caulfield | M. Farrall | R. Gwilliam | S. Potter | A. Gabrielsen | R. Peto | S. Edkins | A. Helgadóttir | J. Peden | S. Ripatti | P. Froguel | D. Bennett | M. Lathrop | H. Ongen | A. Hamsten | A. Silveira | A. Franco‐Cereceda | P. Eriksson | N. Soranzo | G. Assmann | D. Saleheen | H. Watkins | J. Kooner | S. Yusuf | Elizabeth E Gray | G. Dedoussis | R. Clarke | A. Goel | Weihua Zhang | B. Gigante | J. Chambers | K. Leander | James G. Scott | M. Murtaza | S. Parish | L. Folkersen | R. Strawbridge | S. Sivapalaratnam | J. Armitage | Sonia S Anand | J. Sinisalo | J. Sehmi | A. Rasheed | U. Seedorf | G. Tognoni | P. Linksted | J. Hopewell | J. Hager | M. Franzosi | P. Sleight | U. Defaire | N. Shah | P. Frossard | M. Ishaq | L. Bowman | S. Jalilzadeh | M. Delepine | M. Zaidi | M. Samuel | T. Kyriakou | S. Barlera | S. Rust | A. Malarstig | F. Green | N. H. Mallick | K. S. Zaman | J. Öhrvik | R. Marchioli | T. Axelsson | S. Bumpstead | Naveeduddin Ahmed | E. Theodoraki | Salomaa | M. Azhar | A. Offer | F. Gori | G. Olsson | A. Samad | A. Kooner | A. Syvanen | F. Memon | S. Pietri | J. Kastelein | A. Gardezi | M-L Hellánius | J. Engert | A. Franco-Cereceda | Angad S Kooner | Weihua Zhang | J. Scott | A. Goel | M. McCarthy | M. McCarthy | Simon C. Potter | Nabi Shah

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