A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

Authors:
Dr. Dharambir K Sanghera
Dr. Dharambir K Sanghera
University of Oklahoma Health Sciences Center
Professor
Oklahoma City, Oklahoma | United States
Majid Nikpay Anuj Goel Hong-Hee Won Leanne M Hall Christina Willenborg Stavroula Kanoni Danish Saleheen Theodosios Kyriakou Christopher P Nelson Jemma C Hopewell Thomas R Webb Lingyao Zeng Abbas Dehghan Maris Alver Sebastian M Armasu 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 M Lindgren Marja-Liisa Lokki Patrik K Magnusson Nadeem H Mallick Narinder Mehra Thomas Meitinger Fazal-Ur-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 E Stirrups 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 L Adrienne 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 S Hall Anders Hamsten Tamara B Harris Stanley L Hazen 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 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

Nat Genet 2015 Oct 7;47(10):1121-1130. Epub 2015 Sep 7.

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

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.

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http://dx.doi.org/10.1038/ng.3396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589895PMC
October 2015
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References

(Supplied by CrossRef)

T Kessler et al.
Curr. Cardiol. Rep. 2013

CJ O'Donnell et al.
N. Engl. J. Med. 2011

F Wang et al.
Nat. Genet. 2011

R Clarke et al.
N. Engl. J. Med. 2009

AM Bennet et al.
J. Am. Med. Assoc. 2007

M Benn et al.
J. Am. Coll. Cardiol. 2010

JC Cohen et al.
N. Engl. J. Med. 2006

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