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

John F. Peden, Jemma C. Hopewell, Danish Saleheen, John C. Chambers, Jorg Hager, Nicole Soranzo, Rory Collins, John Danesh, Paul Elliott, Martin Farrall, Kathy Stirrups, Weihua Zhang, Anders Hamsten, Sarah Parish, Mark Lathrop, Hugh Watkins, Robert Clarke, Panos Deloukas, Jaspal S. Kooner, Anuj Goel & 82 others Halit Ongen, Rona J. Strawbridge, Simon Heath, Anders Mal̈arstig, Anna Helgadottir, John Öhrvik, Muhammed Murtaza, Simon Potter, Sarah E. Hunt, Marc Delepine, Shapour Jalilzadeh, Tomas Axelsson, Ann Christine Syvanen, Rhian Gwilliam, Suzannah Bumpstead, Emma Gray, Sarah Edkins, Lasse Folkersen, Theodosios Kyriakou, Anders Franco-Cereceda, Anders Gabrielsen, Udo Seedorf, Per Eriksson, Alison Offer, Louise Bowman, Peter Sleight, Jane Armitage, Richard Peto, Goncalo Abecasis, Nabeel Ahmed, Mark Caulfield, Peter Donnelly, Philippe Froguel, Angad S. Kooner, Mark I. McCarthy, Nilesh J. Samani, James Scott, Joban Sehmi, Angela Silveira, Mai Lis Hellánius, Ferdinand M. Van 'T Hooft, Gunnar Olsson, Stephan Rust, Gerd Assmann, Simona Barlera, Gianni Tognoni, Maria Grazia Franzosi, Pamela Linksted, Fiona R. Green, Asif Rasheed, Moazzam Zaidi, Nabi Shah, Maria Samuel, Nadeem H. Mallick, Muhammad Azhar, Khan S. Zaman, Abdus Samad, Mohammad Ishaq, Ali R. Gardezi, Fazal Ur Rehman Memon, Philippe M. Frossard, Tim Spector, Leena Peltonen, Markku S. Nieminen, Juha Sinisalo, Veikko Salomaa, Samuli Ripatti, Derrick Bennett, Karin Leander, Bruna Gigante, Ulf De Faire, Silvia Pietri, Francesca Gori, Roberto Marchioli, Suthesh Sivapalaratnam, John J P Kastelein, Mieke D. Trip, Eirini V. Theodoraki, George V. Dedoussis, Jamie C. Engert, Salim Yusuf, Sonia S. Anand

Research output: Contribution to journalArticle

422 Citations (Scopus)

Abstract

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 -4575,000 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.

Original languageEnglish
Pages (from-to)339-346
Number of pages8
JournalNature Genetics
Volume43
Issue number4
DOIs
Publication statusPublished - Feb 2011

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Genome-Wide Association Study
Coronary Artery Disease
Single Nucleotide Polymorphism
Quantitative Trait Loci
Disease Susceptibility
Meta-Analysis
Population
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Peden, J. F., Hopewell, J. C., Saleheen, D., Chambers, J. C., Hager, J., Soranzo, N., ... Anand, S. S. (2011). A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nature Genetics, 43(4), 339-346. https://doi.org/10.1038/ng.782

A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. / Peden, John F.; Hopewell, Jemma C.; Saleheen, Danish; Chambers, John C.; Hager, Jorg; Soranzo, Nicole; Collins, Rory; Danesh, John; Elliott, Paul; Farrall, Martin; Stirrups, Kathy; Zhang, Weihua; Hamsten, Anders; Parish, Sarah; Lathrop, Mark; Watkins, Hugh; Clarke, Robert; Deloukas, Panos; Kooner, Jaspal S.; Goel, Anuj; Ongen, Halit; Strawbridge, Rona J.; Heath, Simon; Mal̈arstig, Anders; Helgadottir, Anna; Öhrvik, John; Murtaza, Muhammed; Potter, Simon; Hunt, Sarah E.; Delepine, Marc; Jalilzadeh, Shapour; Axelsson, Tomas; Syvanen, Ann Christine; Gwilliam, Rhian; Bumpstead, Suzannah; Gray, Emma; Edkins, Sarah; Folkersen, Lasse; Kyriakou, Theodosios; Franco-Cereceda, Anders; Gabrielsen, Anders; Seedorf, Udo; Eriksson, Per; Offer, Alison; Bowman, Louise; Sleight, Peter; Armitage, Jane; Peto, Richard; Abecasis, Goncalo; Ahmed, Nabeel; Caulfield, Mark; Donnelly, Peter; Froguel, Philippe; Kooner, Angad S.; McCarthy, Mark I.; Samani, Nilesh J.; Scott, James; Sehmi, Joban; Silveira, Angela; Hellánius, Mai Lis; Van 'T Hooft, Ferdinand M.; Olsson, Gunnar; Rust, Stephan; Assmann, Gerd; Barlera, Simona; Tognoni, Gianni; Franzosi, Maria Grazia; Linksted, Pamela; Green, Fiona R.; Rasheed, Asif; Zaidi, Moazzam; Shah, Nabi; Samuel, Maria; Mallick, Nadeem H.; Azhar, Muhammad; Zaman, Khan S.; Samad, Abdus; Ishaq, Mohammad; Gardezi, Ali R.; Memon, Fazal Ur Rehman; Frossard, Philippe M.; Spector, Tim; Peltonen, Leena; Nieminen, Markku S.; Sinisalo, Juha; Salomaa, Veikko; Ripatti, Samuli; Bennett, Derrick; Leander, Karin; Gigante, Bruna; De Faire, Ulf; Pietri, Silvia; Gori, Francesca; Marchioli, Roberto; Sivapalaratnam, Suthesh; Kastelein, John J P; Trip, Mieke D.; Theodoraki, Eirini V.; Dedoussis, George V.; Engert, Jamie C.; Yusuf, Salim; Anand, Sonia S.

In: Nature Genetics, Vol. 43, No. 4, 02.2011, p. 339-346.

Research output: Contribution to journalArticle

Peden, JF, Hopewell, JC, Saleheen, D, Chambers, JC, Hager, J, Soranzo, N, Collins, R, Danesh, J, Elliott, P, Farrall, M, Stirrups, K, Zhang, W, Hamsten, A, Parish, S, Lathrop, M, Watkins, H, Clarke, R, Deloukas, P, Kooner, JS, Goel, A, Ongen, H, Strawbridge, RJ, Heath, S, Mal̈arstig, A, Helgadottir, A, Öhrvik, J, Murtaza, M, Potter, S, Hunt, SE, Delepine, M, Jalilzadeh, S, Axelsson, T, Syvanen, AC, Gwilliam, R, Bumpstead, S, Gray, E, Edkins, S, Folkersen, L, Kyriakou, T, Franco-Cereceda, A, Gabrielsen, A, Seedorf, U, Eriksson, P, Offer, A, Bowman, L, Sleight, P, Armitage, J, Peto, R, Abecasis, G, Ahmed, N, Caulfield, M, Donnelly, P, Froguel, P, Kooner, AS, McCarthy, MI, Samani, NJ, Scott, J, Sehmi, J, Silveira, A, Hellánius, ML, Van 'T Hooft, FM, Olsson, G, Rust, S, Assmann, G, Barlera, S, Tognoni, G, Franzosi, MG, Linksted, P, Green, FR, Rasheed, A, Zaidi, M, Shah, N, Samuel, M, Mallick, NH, Azhar, M, Zaman, KS, Samad, A, Ishaq, M, Gardezi, AR, Memon, FUR, Frossard, PM, Spector, T, Peltonen, L, Nieminen, MS, Sinisalo, J, Salomaa, V, Ripatti, S, Bennett, D, Leander, K, Gigante, B, De Faire, U, Pietri, S, Gori, F, Marchioli, R, Sivapalaratnam, S, Kastelein, JJP, Trip, MD, Theodoraki, EV, Dedoussis, GV, Engert, JC, Yusuf, S & Anand, SS 2011, 'A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease', Nature Genetics, vol. 43, no. 4, pp. 339-346. https://doi.org/10.1038/ng.782
Peden, John F. ; Hopewell, Jemma C. ; Saleheen, Danish ; Chambers, John C. ; Hager, Jorg ; Soranzo, Nicole ; Collins, Rory ; Danesh, John ; Elliott, Paul ; Farrall, Martin ; Stirrups, Kathy ; Zhang, Weihua ; Hamsten, Anders ; Parish, Sarah ; Lathrop, Mark ; Watkins, Hugh ; Clarke, Robert ; Deloukas, Panos ; Kooner, Jaspal S. ; Goel, Anuj ; Ongen, Halit ; Strawbridge, Rona J. ; Heath, Simon ; Mal̈arstig, Anders ; Helgadottir, Anna ; Öhrvik, John ; Murtaza, Muhammed ; Potter, Simon ; Hunt, Sarah E. ; Delepine, Marc ; Jalilzadeh, Shapour ; Axelsson, Tomas ; Syvanen, Ann Christine ; Gwilliam, Rhian ; Bumpstead, Suzannah ; Gray, Emma ; Edkins, Sarah ; Folkersen, Lasse ; Kyriakou, Theodosios ; Franco-Cereceda, Anders ; Gabrielsen, Anders ; Seedorf, Udo ; Eriksson, Per ; Offer, Alison ; Bowman, Louise ; Sleight, Peter ; Armitage, Jane ; Peto, Richard ; Abecasis, Goncalo ; Ahmed, Nabeel ; Caulfield, Mark ; Donnelly, Peter ; Froguel, Philippe ; Kooner, Angad S. ; McCarthy, Mark I. ; Samani, Nilesh J. ; Scott, James ; Sehmi, Joban ; Silveira, Angela ; Hellánius, Mai Lis ; Van 'T Hooft, Ferdinand M. ; Olsson, Gunnar ; Rust, Stephan ; Assmann, Gerd ; Barlera, Simona ; Tognoni, Gianni ; Franzosi, Maria Grazia ; Linksted, Pamela ; Green, Fiona R. ; Rasheed, Asif ; Zaidi, Moazzam ; Shah, Nabi ; Samuel, Maria ; Mallick, Nadeem H. ; Azhar, Muhammad ; Zaman, Khan S. ; Samad, Abdus ; Ishaq, Mohammad ; Gardezi, Ali R. ; Memon, Fazal Ur Rehman ; Frossard, Philippe M. ; Spector, Tim ; Peltonen, Leena ; Nieminen, Markku S. ; Sinisalo, Juha ; Salomaa, Veikko ; Ripatti, Samuli ; Bennett, Derrick ; Leander, Karin ; Gigante, Bruna ; De Faire, Ulf ; Pietri, Silvia ; Gori, Francesca ; Marchioli, Roberto ; Sivapalaratnam, Suthesh ; Kastelein, John J P ; Trip, Mieke D. ; Theodoraki, Eirini V. ; Dedoussis, George V. ; Engert, Jamie C. ; Yusuf, Salim ; Anand, Sonia S. / A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. In: Nature Genetics. 2011 ; Vol. 43, No. 4. pp. 339-346.
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T1 - A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

AU - Peden, John F.

AU - Hopewell, Jemma C.

AU - Saleheen, Danish

AU - Chambers, John C.

AU - Hager, Jorg

AU - Soranzo, Nicole

AU - Collins, Rory

AU - Danesh, John

AU - Elliott, Paul

AU - Farrall, Martin

AU - Stirrups, Kathy

AU - Zhang, Weihua

AU - Hamsten, Anders

AU - Parish, Sarah

AU - Lathrop, Mark

AU - Watkins, Hugh

AU - Clarke, Robert

AU - Deloukas, Panos

AU - Kooner, Jaspal S.

AU - Goel, Anuj

AU - Ongen, Halit

AU - Strawbridge, Rona J.

AU - Heath, Simon

AU - Mal̈arstig, Anders

AU - Helgadottir, Anna

AU - Öhrvik, John

AU - Murtaza, Muhammed

AU - Potter, Simon

AU - Hunt, Sarah E.

AU - Delepine, Marc

AU - Jalilzadeh, Shapour

AU - Axelsson, Tomas

AU - Syvanen, Ann Christine

AU - Gwilliam, Rhian

AU - Bumpstead, Suzannah

AU - Gray, Emma

AU - Edkins, Sarah

AU - Folkersen, Lasse

AU - Kyriakou, Theodosios

AU - Franco-Cereceda, Anders

AU - Gabrielsen, Anders

AU - Seedorf, Udo

AU - Eriksson, Per

AU - Offer, Alison

AU - Bowman, Louise

AU - Sleight, Peter

AU - Armitage, Jane

AU - Peto, Richard

AU - Abecasis, Goncalo

AU - Ahmed, Nabeel

AU - Caulfield, Mark

AU - Donnelly, Peter

AU - Froguel, Philippe

AU - Kooner, Angad S.

AU - McCarthy, Mark I.

AU - Samani, Nilesh J.

AU - Scott, James

AU - Sehmi, Joban

AU - Silveira, Angela

AU - Hellánius, Mai Lis

AU - Van 'T Hooft, Ferdinand M.

AU - Olsson, Gunnar

AU - Rust, Stephan

AU - Assmann, Gerd

AU - Barlera, Simona

AU - Tognoni, Gianni

AU - Franzosi, Maria Grazia

AU - Linksted, Pamela

AU - Green, Fiona R.

AU - Rasheed, Asif

AU - Zaidi, Moazzam

AU - Shah, Nabi

AU - Samuel, Maria

AU - Mallick, Nadeem H.

AU - Azhar, Muhammad

AU - Zaman, Khan S.

AU - Samad, Abdus

AU - Ishaq, Mohammad

AU - Gardezi, Ali R.

AU - Memon, Fazal Ur Rehman

AU - Frossard, Philippe M.

AU - Spector, Tim

AU - Peltonen, Leena

AU - Nieminen, Markku S.

AU - Sinisalo, Juha

AU - Salomaa, Veikko

AU - Ripatti, Samuli

AU - Bennett, Derrick

AU - Leander, Karin

AU - Gigante, Bruna

AU - De Faire, Ulf

AU - Pietri, Silvia

AU - Gori, Francesca

AU - Marchioli, Roberto

AU - Sivapalaratnam, Suthesh

AU - Kastelein, John J P

AU - Trip, Mieke D.

AU - Theodoraki, Eirini V.

AU - Dedoussis, George V.

AU - Engert, Jamie C.

AU - Yusuf, Salim

AU - Anand, Sonia S.

PY - 2011/2

Y1 - 2011/2

N2 - 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 -4575,000 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.

AB - 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 -4575,000 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.

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