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Title: A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease
Authors: Nikpay, M.
Goel, A.
Won, H.-H.
Hall, L. M.
Willenborg, C.
Kanoni, S.
Saleheen, D.
Kyriakou, T.
Nelson, Christopher Paul
Hopewell, J. C.
Webb, T. R.
van Zuydam, N. R.
Anand, S. S.
Bertram, L.
Beutner, F.
Dedoussis, G.
Frossard, P.
Gauguier, D.
Goodall, A. H.
Gottesman, O.
Haber, M.
Franco, O. H.
Han, B. -G.
Huang, J.
Jalilzadeh, S.
Kessler, T.
König, I. R.
Lannfelt, L.
Lieb, W.
Lind, L.
Lindgren, C. M.
Lokki, M.-L.
Franzosi, M. G.
Magnusson, P. K.
Mallick, N. H.
Mehra, N.
Meitinger, T.
Memon, F.-U.-R.
Morris, A. P.
Nieminen, M. S.
Pedersen, N. L.
Peters, A.
Rallidis, L. S.
Granger, C. B.
Rasheed, A.
Samuel, M.
Shah, S. H.
Sinisalo, J.
Stirrups, K. E.
Trompet, S.
Wang, L.
Zaman, K. S.
Ardissino, D.
Boerwinkle, E.
Gu, D.
Borecki, I. B.
Bottinger, E. P.
Buring, J. E.
Chambers, J. C.
Collins, R.
Cupples, L. A.
Danesh, J.
Demuth, I.
Elosua, R.
Epstein, S. E.
Gudnason, V.
Esko, T.
Feitosa, M. F.
Hall, A. S.
Hamsten, A.
Harris, T. B.
Hazen, S. L.
Hengstenberg, C.
Zeng, L.
Hofman, A.
Ingelsson, E.
Iribarren, C.
Jukema, J. W.
Karhunen, P. J.
Kim, B. -.J.
Kooner, J. S.
Kullo, I. J.
Lehtimäki, T.
Loos, R. J. F.
Dehghan, A.
Melander, O.
Metspalu, A.
März, W.
Palmer, C. N.
Perola, M.
Quertermous, T.
Rader, D. J.
Ridker, P. M.
Ripatti, S.
Roberts, R.
Alver, M.
Salomaa, V.
Sanghera, D. K.
Schwartz, S. M.
Seedorf, U.
Stewart, A. F.
Stott, D. J.
Thiery, J.
Zalloua, P. A.
O'Donnell, C. J.
Reilly, M. P.
Armasu, S. M.
Assimes, T. L.
Thompson, J. R.
Erdmann, J.
Clarke, R.
Watkins, H.
Kathiresan, S.
McPherson, R.
Deloukas, P.
Schunkert, H.
Samani, N. J.
Auro, K.
Farrall, M.
CARDIoGRAMplusC4D Consortium
Bjonnes, A.
Chasman, D. I.
Chen, S.
Ford, I.
Franceschini, N.
Gieger, C.
Grace, C.
Gustafsson, S.
Huang, J.
Hwang, S.-J.
Kim, Y. K.
Kleber, M. E.
Lau, K. W.
Lu, X.
Lu, Y.
Lyytikäinen, L.-P.
Mihailov, E.
Morrison, A. C.
Pervjakova, N.
Qu, L.
Rose, L. M.
Salfati, E.
Saxena, R.
Scholz, M.
Smith, A. V.
Tikkanen, E.
Uitterlinden, A.
Yang, X.
Zhang, W.
Zhao, W.
de Andrade, M.
de Vries, P. S.
First Published: 14-Sep-2015
Publisher: Nature Publishing Group
Citation: Nature Genetics, 2015, 47 (10), pp. 1121-1130
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.
DOI Link: 10.1038/ng.3396
ISSN: 1061-4036
eISSN: 1546-1718
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, Nature Publishing Group. Deposited with reference to the publisher’s open access archiving policy.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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