A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Majid Nikpay; Anuj Goel; Hong Hee Won; Leanne M. Hall; Christina Willenborg; Stavroula Kanoni; Danish Saleheen; Theodosios Kyriakou; Christopher P. Nelson; Jemma CHopewell; Thomas R. Webb; Lingyao Zeng; Abbas Dehghan; Maris Alver; Sebastian MArmasu; Kirsi Auro; Andrew Bjonnes; Daniel I. Chasman; Shufeng Chen; Ian Ford; Nora Franceschini; Christian Gieger; Christopher Grace; Stefan Gustafsson; Jie Huang; Shih Jen Hwang; Yun Kyoung Kim; Marcus E. Kleber; King Wai Lau; Xiangfeng Lu; Yingchang Lu; Leo Pekka Lyytikäinen; Evelin Mihailov; Alanna C. Morrison; Natalia Pervjakova; Liming Qu; Lynda M. Rose; Elias Salfati; Richa Saxena; Markus Scholz; Albert V. Smith; Emmi Tikkanen; Andre Uitterlinden; Xueli Yang; Weihua Zhang; Wei Zhao; Mariza De Andrade; Paul S. De Vries; Natalie R. Van Zuydam; Sonia S. Anand; Lars Bertram; Frank Beutner; George Dedoussis; Philippe Frossard; Dominique Gauguier; Alison H. Goodall; Omri Gottesman; Marc Haber; Bok Ghee Han; Jianfeng Huang; Shapour Jalilzadeh; Thorsten Kessler; Inke R. König; Lars Lannfelt; Wolfgang Lieb; Lars Lind; Cecilia MLindgren; Marja Liisa Lokki; Patrik K. Magnusson; Nadeem H. Mallick; Narinder Mehra; Thomas Meitinger; Fazal Uur Rehman Memon; Andrew P. Morris; Markku S. Nieminen; Nancy L. Pedersen; Annette Peters; Loukianos S. Rallidis; Asif Rasheed; Maria Samuel; Svati H. Shah; Juha Sinisalo; Kathleen EStirrups; Stella Trompet; Laiyuan Wang; Khan S. Zaman; Diego Ardissino; Eric Boerwinkle; Ingrid B. Borecki; Erwin P. Bottinger; Julie E. Buring; John C. Chambers; Rory Collins; Ladrienne Cupples; John Danesh; Ilja Demuth; Roberto Elosua; Stephen E. Epstein; Tõnu Esko; Mary F. Feitosa; Oscar H. Franco; Maria Grazia Franzosi; Christopher B. Granger; Dongfeng Gu; Vilmundur Gudnason; Alistair SHall; Anders Hamsten; Tamara B. Harris; Stanley LHazen; Christian Hengstenberg; Albert Hofman; Erik Ingelsson; Carlos Iribarren; J. Wouter Jukema; Pekka J. Karhunen; Bong Jo Kim; Jaspal S. Kooner; Iftikhar J. Kullo; Terho Lehtimäki; Ruth J.F. Loos; Olle Melander; Andres Metspalu; Winfried März; Colin N. Palmer; Markus Perola; Thomas Quertermous; Daniel J. Rader; Paul M. Ridker; Samuli Ripatti; Robert Roberts; Veikko Salomaa; Dharambir K. Sanghera; Stephen M. Schwartz; Udo Seedorf; Alexandre F. Stewart; David J. Stott; Joachim Thiery; Pierre A. Zalloua; Christopher J. O'Donnell; Muredach P. Reilly; Themistocles L. Assimes; John R. Thompson; Jeanette Erdmann; Robert Clarke; Hugh Watkins; Sekar Kathiresan; Ruth McPherson; Panos Deloukas; Heribert Schunkert; Nilesh J. Samani; Martin Farrall

doi:10.1038/ng.3396

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Majid Nikpay
, Anuj Goel
, Hong Hee Won
, Leanne M. Hall
, Christina Willenborg
, Stavroula Kanoni
, Danish Saleheen
, Theodosios Kyriakou
, Christopher P. Nelson
, Jemma CHopewell
, Thomas R. Webb
, Lingyao Zeng
, Abbas Dehghan
, Maris Alver
, Sebastian MArmasu
, Kirsi Auro
, Andrew Bjonnes
, Daniel I. Chasman
, Shufeng Chen
, Ian Ford

Nora Franceschini, Christian Gieger, Christopher Grace, Stefan Gustafsson, Jie Huang, Shih Jen Hwang, Yun Kyoung Kim, Marcus E. Kleber, King Wai Lau, Xiangfeng Lu, Yingchang Lu, Leo Pekka Lyytikäinen, Evelin Mihailov, Alanna C. Morrison, Natalia Pervjakova, Liming Qu, Lynda M. Rose, Elias Salfati, Richa Saxena, Markus Scholz, Albert V. Smith, Emmi Tikkanen, Andre Uitterlinden, Xueli Yang, Weihua Zhang, Wei Zhao, Mariza De Andrade, Paul S. De Vries, Natalie R. Van Zuydam, Sonia S. Anand, Lars Bertram, Frank Beutner, George Dedoussis, Philippe Frossard, Dominique Gauguier, Alison H. Goodall, Omri Gottesman, Marc Haber, Bok Ghee Han, Jianfeng Huang, Shapour Jalilzadeh, Thorsten Kessler, Inke R. König, Lars Lannfelt, Wolfgang Lieb, Lars Lind, Cecilia MLindgren, Marja Liisa Lokki, Patrik K. Magnusson, Nadeem H. Mallick, Narinder Mehra, Thomas Meitinger, Fazal Uur Rehman Memon, Andrew P. Morris, Markku S. Nieminen, Nancy L. Pedersen, Annette Peters, Loukianos S. Rallidis, Asif Rasheed, Maria Samuel, Svati H. Shah, Juha Sinisalo, Kathleen EStirrups, Stella Trompet, Laiyuan Wang, Khan S. Zaman, Diego Ardissino, Eric Boerwinkle, Ingrid B. Borecki, Erwin P. Bottinger, Julie E. Buring, John C. Chambers, Rory Collins, Ladrienne Cupples, John Danesh, Ilja Demuth, Roberto Elosua, Stephen E. Epstein, Tõnu Esko, Mary F. Feitosa, Oscar H. Franco, Maria Grazia Franzosi, Christopher B. Granger, Dongfeng Gu, Vilmundur Gudnason, Alistair SHall, Anders Hamsten, Tamara B. Harris, Stanley LHazen, Christian Hengstenberg, Albert Hofman, Erik Ingelsson, Carlos Iribarren, J. Wouter Jukema, Pekka J. Karhunen, Bong Jo Kim, Jaspal S. Kooner, Iftikhar J. Kullo, Terho Lehtimäki, Ruth J.F. Loos, Olle Melander, Andres Metspalu, Winfried März, Colin N. Palmer, Markus Perola, Thomas Quertermous, Daniel J. Rader, Paul M. Ridker, Samuli Ripatti, Robert Roberts, Veikko Salomaa, Dharambir K. Sanghera, Stephen M. Schwartz, Udo Seedorf, Alexandre F. Stewart, David J. Stott, Joachim Thiery, Pierre A. Zalloua, Christopher J. O'Donnell, Muredach P. Reilly, Themistocles L. Assimes, John R. Thompson, Jeanette Erdmann, Robert Clarke, Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Panos Deloukas, Heribert Schunkert, Nilesh J. Samani, Martin Farrall

University of Ottawa
University of Oxford
Broad Institute
Massachusetts General Hospital
Harvard University
University of Leicester
University of Lübeck
German Centre for Cardiovascular Research
Queen Mary University of London
University of Pennsylvania
Center for Non-Communicable Diseases
University Hospitals of Leicester NHS Trust
Technical University of Munich
Erasmus University Rotterdam
University of Tartu
University of Tartu
Mayo Clinic Rochester, MN
National Institute for Health and Welfare
University of Helsinki
Brigham and Women’s Hospital
Chinese Academy of Medical Sciences
University of Glasgow
University of North Carolina at Chapel Hill
Helmholtz Zentrum München - German Research Center for Environmental Health
Uppsala University
Wellcome Sanger Institute
Boston University's Framingham Heart Study
Boston University
Korea National Institute of Health
Heidelberg University
Icahn School of Medicine at Mount Sinai
Fimlab Laboratories
Tampere University
University of Texas Health Science Center at Houston
Stanford University
Leipzig University
LIFE Research Center of Civilization Diseases
Icelandic Heart Association
University of Iceland
Imperial College London
London North West University Healthcare NHS Trust
University of Dundee
McMaster University
Harokopio University
Centre de Recherche des Cordeliers
Lebanese American University
Kiel University
Karolinska Institutet
University of Health Sciences Lahore
All India Institute of Medical Sciences, New Delhi
Red Crescent Institute of Cardiology
University of Liverpool
Helsinki University Hospital
National and Kapodistrian University of Athens
Duke University
University of Cambridge
Leiden University
Chinese National Human Genome Center
National Institute of Cardiovascular Diseases (NICVD)
University of Parma
ASTC: Associazione per lo Studio Della Trombosi in Cardiologia
Baylor College of Medicine
Washington University St. Louis
Imperial College Healthcare NHS Trust
Charité – Universitätsmedizin Berlin
Hospital del Mar
Washington Hospital Center
Boston Children's Hospital
IRCCS Multimedica - Milano
University of Leeds
National Institutes of Health
Cleveland Clinic Foundation
Kaiser Permanente
Durrer Center for Cardiogenetic Research
Royal Netherlands Academy of Arts and Sciences
Lund University
SYNLAB International GmbH
Medical University of Graz
University of Oklahoma
Oklahoma Center for Neuroscience
Fred Hutchinson Cancer Research Center
University of Washington
University of Hamburg
King Abdulaziz University

Research output: Contribution to journal › Article › peer-review

1980 Scopus citations

Abstract

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

Original language	English
Pages (from-to)	1121-1130
Number of pages	10
Journal	Nature Genetics
Volume	47
Issue number	10
DOIs	https://doi.org/10.1038/ng.3396
State	Published - 29 Sep 2015
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/ng.3396

Cite this

Nikpay, M., Goel, A., Won, H. H., Hall, L. M., Willenborg, C., Kanoni, S., Saleheen, D., Kyriakou, T., Nelson, C. P., CHopewell, J., Webb, T. R., Zeng, L., Dehghan, A., Alver, M., MArmasu, S., Auro, K., Bjonnes, A., Chasman, D. I., Chen, S., ... Farrall, M. (2015). A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nature Genetics, 47(10), 1121-1130. https://doi.org/10.1038/ng.3396

@article{f0f3cd501de1411d9941754b649f038a,

title = "A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease",

abstract = "Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.",

author = "Majid Nikpay and Anuj Goel and Won, \{Hong Hee\} and Hall, \{Leanne M.\} and Christina Willenborg and Stavroula Kanoni and Danish Saleheen and Theodosios Kyriakou and Nelson, \{Christopher P.\} and Jemma CHopewell and Webb, \{Thomas R.\} and Lingyao Zeng and Abbas Dehghan and Maris Alver and Sebastian MArmasu and Kirsi Auro and Andrew Bjonnes and Chasman, \{Daniel I.\} and Shufeng Chen and Ian Ford and Nora Franceschini and Christian Gieger and Christopher Grace and Stefan Gustafsson and Jie Huang and Hwang, \{Shih Jen\} and Kim, \{Yun Kyoung\} and Kleber, \{Marcus E.\} and Lau, \{King Wai\} and Xiangfeng Lu and Yingchang Lu and Lyytik{\"a}inen, \{Leo Pekka\} and Evelin Mihailov and Morrison, \{Alanna C.\} and Natalia Pervjakova and Liming Qu and Rose, \{Lynda M.\} and Elias Salfati and Richa Saxena and Markus Scholz and Smith, \{Albert V.\} and Emmi Tikkanen and Andre Uitterlinden and Xueli Yang and Weihua Zhang and Wei Zhao and \{De Andrade\}, Mariza and \{De Vries\}, \{Paul S.\} and \{Van Zuydam\}, \{Natalie R.\} and Anand, \{Sonia S.\} and Lars Bertram and Frank Beutner and George Dedoussis and Philippe Frossard and Dominique Gauguier and Goodall, \{Alison H.\} and Omri Gottesman and Marc Haber and Han, \{Bok Ghee\} and Jianfeng Huang and Shapour Jalilzadeh and Thorsten Kessler and K{\"o}nig, \{Inke R.\} and Lars Lannfelt and Wolfgang Lieb and Lars Lind and Cecilia MLindgren and Lokki, \{Marja Liisa\} and Magnusson, \{Patrik K.\} and Mallick, \{Nadeem H.\} and Narinder Mehra and Thomas Meitinger and Memon, \{Fazal Uur Rehman\} and Morris, \{Andrew P.\} and Nieminen, \{Markku S.\} and Pedersen, \{Nancy L.\} and Annette Peters and Rallidis, \{Loukianos S.\} and Asif Rasheed and Maria Samuel and Shah, \{Svati H.\} and Juha Sinisalo and Kathleen EStirrups and Stella Trompet and Laiyuan Wang and Zaman, \{Khan S.\} and Diego Ardissino and Eric Boerwinkle and Borecki, \{Ingrid B.\} and Bottinger, \{Erwin P.\} and Buring, \{Julie E.\} and Chambers, \{John C.\} and Rory Collins and Ladrienne Cupples and John Danesh and Ilja Demuth and Roberto Elosua and Epstein, \{Stephen E.\} and T{\~o}nu Esko and Feitosa, \{Mary F.\} and Franco, \{Oscar H.\} and Franzosi, \{Maria Grazia\} and Granger, \{Christopher B.\} and Dongfeng Gu and Vilmundur Gudnason and Alistair SHall and Anders Hamsten and Harris, \{Tamara B.\} and Stanley LHazen and Christian Hengstenberg and Albert Hofman and Erik Ingelsson and Carlos Iribarren and Jukema, \{J. Wouter\} and Karhunen, \{Pekka J.\} and Kim, \{Bong Jo\} and Kooner, \{Jaspal S.\} and Kullo, \{Iftikhar J.\} and Terho Lehtim{\"a}ki and Loos, \{Ruth J.F.\} and Olle Melander and Andres Metspalu and Winfried M{\"a}rz and Palmer, \{Colin N.\} and Markus Perola and Thomas Quertermous and Rader, \{Daniel J.\} and Ridker, \{Paul M.\} and Samuli Ripatti and Robert Roberts and Veikko Salomaa and Sanghera, \{Dharambir K.\} and Schwartz, \{Stephen M.\} and Udo Seedorf and Stewart, \{Alexandre F.\} and Stott, \{David J.\} and Joachim Thiery and Zalloua, \{Pierre A.\} and O'Donnell, \{Christopher J.\} and Reilly, \{Muredach P.\} and Assimes, \{Themistocles L.\} and Thompson, \{John R.\} and Jeanette Erdmann and Robert Clarke and Hugh Watkins and Sekar Kathiresan and Ruth McPherson and Panos Deloukas and Heribert Schunkert and Samani, \{Nilesh J.\} and Martin Farrall",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = sep,

day = "29",

doi = "10.1038/ng.3396",

language = "English",

volume = "47",

pages = "1121--1130",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Nikpay, M, Goel, A, Won, HH, Hall, LM, Willenborg, C, Kanoni, S, Saleheen, D, Kyriakou, T, Nelson, CP, CHopewell, J, Webb, TR, Zeng, L, Dehghan, A, Alver, M, MArmasu, S, Auro, K, Bjonnes, A, Chasman, DI, Chen, S, Ford, I, Franceschini, N, Gieger, C, Grace, C, Gustafsson, S, Huang, J, Hwang, SJ, Kim, YK, Kleber, ME, Lau, KW, Lu, X, Lu, Y, Lyytikäinen, LP, Mihailov, E, Morrison, AC, Pervjakova, N, Qu, L, Rose, LM, Salfati, E, Saxena, R, Scholz, M, Smith, AV, Tikkanen, E, Uitterlinden, A, Yang, X, Zhang, W, Zhao, W, De Andrade, M, De Vries, PS, Van Zuydam, NR, Anand, SS, Bertram, L, Beutner, F, Dedoussis, G, Frossard, P, Gauguier, D, Goodall, AH, Gottesman, O, Haber, M, Han, BG, Huang, J, Jalilzadeh, S, Kessler, T, König, IR, Lannfelt, L, Lieb, W, Lind, L, MLindgren, C, Lokki, ML, Magnusson, PK, Mallick, NH, Mehra, N, Meitinger, T, Memon, FUR, Morris, AP, Nieminen, MS, Pedersen, NL, Peters, A, Rallidis, LS, Rasheed, A, Samuel, M, Shah, SH, Sinisalo, J, EStirrups, K, Trompet, S, Wang, L, Zaman, KS, Ardissino, D, Boerwinkle, E, Borecki, IB, Bottinger, EP, Buring, JE, Chambers, JC, Collins, R, Cupples, L, Danesh, J, Demuth, I, Elosua, R, Epstein, SE, Esko, T, Feitosa, MF, Franco, OH, Franzosi, MG, Granger, CB, Gu, D, Gudnason, V, SHall, A, Hamsten, A, Harris, TB, LHazen, S, Hengstenberg, C, Hofman, A, Ingelsson, E, Iribarren, C, Jukema, JW, Karhunen, PJ, Kim, BJ, Kooner, JS, Kullo, IJ, Lehtimäki, T, Loos, RJF, Melander, O, Metspalu, A, März, W, Palmer, CN, Perola, M, Quertermous, T, Rader, DJ, Ridker, PM, Ripatti, S, Roberts, R, Salomaa, V, Sanghera, DK, Schwartz, SM, Seedorf, U, Stewart, AF, Stott, DJ, Thiery, J, Zalloua, PA, O'Donnell, CJ, Reilly, MP, Assimes, TL, Thompson, JR, Erdmann, J, Clarke, R, Watkins, H, Kathiresan, S, McPherson, R, Deloukas, P, Schunkert, H, Samani, NJ & Farrall, M 2015, 'A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease', Nature Genetics, vol. 47, no. 10, pp. 1121-1130. https://doi.org/10.1038/ng.3396

TY - JOUR

T1 - A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

AU - Nikpay, Majid

AU - Goel, Anuj

AU - Won, Hong Hee

AU - Hall, Leanne M.

AU - Willenborg, Christina

AU - Kanoni, Stavroula

AU - Saleheen, Danish

AU - Kyriakou, Theodosios

AU - Nelson, Christopher P.

AU - CHopewell, Jemma

AU - Webb, Thomas R.

AU - Zeng, Lingyao

AU - Dehghan, Abbas

AU - Alver, Maris

AU - MArmasu, Sebastian

AU - Auro, Kirsi

AU - Bjonnes, Andrew

AU - Chasman, Daniel I.

AU - Chen, Shufeng

AU - Ford, Ian

AU - Franceschini, Nora

AU - Gieger, Christian

AU - Grace, Christopher

AU - Gustafsson, Stefan

AU - Huang, Jie

AU - Hwang, Shih Jen

AU - Kim, Yun Kyoung

AU - Kleber, Marcus E.

AU - Lau, King Wai

AU - Lu, Xiangfeng

AU - Lu, Yingchang

AU - Lyytikäinen, Leo Pekka

AU - Mihailov, Evelin

AU - Morrison, Alanna C.

AU - Pervjakova, Natalia

AU - Qu, Liming

AU - Rose, Lynda M.

AU - Salfati, Elias

AU - Saxena, Richa

AU - Scholz, Markus

AU - Smith, Albert V.

AU - Tikkanen, Emmi

AU - Uitterlinden, Andre

AU - Yang, Xueli

AU - Zhang, Weihua

AU - Zhao, Wei

AU - De Andrade, Mariza

AU - De Vries, Paul S.

AU - Van Zuydam, Natalie R.

AU - Anand, Sonia S.

AU - Bertram, Lars

AU - Beutner, Frank

AU - Dedoussis, George

AU - Frossard, Philippe

AU - Gauguier, Dominique

AU - Goodall, Alison H.

AU - Gottesman, Omri

AU - Haber, Marc

AU - Han, Bok Ghee

AU - Huang, Jianfeng

AU - Jalilzadeh, Shapour

AU - Kessler, Thorsten

AU - König, Inke R.

AU - Lannfelt, Lars

AU - Lieb, Wolfgang

AU - Lind, Lars

AU - MLindgren, Cecilia

AU - Lokki, Marja Liisa

AU - Magnusson, Patrik K.

AU - Mallick, Nadeem H.

AU - Mehra, Narinder

AU - Meitinger, Thomas

AU - Memon, Fazal Uur Rehman

AU - Morris, Andrew P.

AU - Nieminen, Markku S.

AU - Pedersen, Nancy L.

AU - Peters, Annette

AU - Rallidis, Loukianos S.

AU - Rasheed, Asif

AU - Samuel, Maria

AU - Shah, Svati H.

AU - Sinisalo, Juha

AU - EStirrups, Kathleen

AU - Trompet, Stella

AU - Wang, Laiyuan

AU - Zaman, Khan S.

AU - Ardissino, Diego

AU - Boerwinkle, Eric

AU - Borecki, Ingrid B.

AU - Bottinger, Erwin P.

AU - Buring, Julie E.

AU - Chambers, John C.

AU - Collins, Rory

AU - Cupples, Ladrienne

AU - Danesh, John

AU - Demuth, Ilja

AU - Elosua, Roberto

AU - Epstein, Stephen E.

AU - Esko, Tõnu

AU - Feitosa, Mary F.

AU - Franco, Oscar H.

AU - Franzosi, Maria Grazia

AU - Granger, Christopher B.

AU - Gu, Dongfeng

AU - Gudnason, Vilmundur

AU - SHall, Alistair

AU - Hamsten, Anders

AU - Harris, Tamara B.

AU - LHazen, Stanley

AU - Hengstenberg, Christian

AU - Hofman, Albert

AU - Ingelsson, Erik

AU - Iribarren, Carlos

AU - Jukema, J. Wouter

AU - Karhunen, Pekka J.

AU - Kim, Bong Jo

AU - Kooner, Jaspal S.

AU - Kullo, Iftikhar J.

AU - Lehtimäki, Terho

AU - Loos, Ruth J.F.

AU - Melander, Olle

AU - Metspalu, Andres

AU - März, Winfried

AU - Palmer, Colin N.

AU - Perola, Markus

AU - Quertermous, Thomas

AU - Rader, Daniel J.

AU - Ridker, Paul M.

AU - Ripatti, Samuli

AU - Roberts, Robert

AU - Salomaa, Veikko

AU - Sanghera, Dharambir K.

AU - Schwartz, Stephen M.

AU - Seedorf, Udo

AU - Stewart, Alexandre F.

AU - Stott, David J.

AU - Thiery, Joachim

AU - Zalloua, Pierre A.

AU - O'Donnell, Christopher J.

AU - Reilly, Muredach P.

AU - Assimes, Themistocles L.

AU - Thompson, John R.

AU - Erdmann, Jeanette

AU - Clarke, Robert

AU - Watkins, Hugh

AU - Kathiresan, Sekar

AU - McPherson, Ruth

AU - Deloukas, Panos

AU - Schunkert, Heribert

AU - Samani, Nilesh J.

AU - Farrall, Martin

PY - 2015/9/29

Y1 - 2015/9/29

N2 - Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

AB - Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

UR - https://www.scopus.com/pages/publications/84942987885

U2 - 10.1038/ng.3396

DO - 10.1038/ng.3396

M3 - Article

C2 - 26343387

AN - SCOPUS:84942987885

SN - 1061-4036

VL - 47

SP - 1121

EP - 1130

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

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