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

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journal contribution
posted on 23.08.2017, 14:49 by M. Nikpay, A. Goel, H.-H. Won, L. M. Hall, C. Willenborg, S. Kanoni, D. Saleheen, T. Kyriakou, Christopher Paul Nelson, J. C. Hopewell, T. R. Webb, N. R. van Zuydam, S. S. Anand, L. Bertram, F. Beutner, G. Dedoussis, P. Frossard, D. Gauguier, A. H. Goodall, O. Gottesman, M. Haber, O. H. Franco, B. -G. Han, J. Huang, S. Jalilzadeh, T. Kessler, I. R. König, L. Lannfelt, W. Lieb, L. Lind, C. M. Lindgren, M.-L. Lokki, M. G. Franzosi, P. K. Magnusson, N. H. Mallick, N. Mehra, T. Meitinger, F.-U.-R. Memon, A. P. Morris, M. S. Nieminen, N. L. Pedersen, A. Peters, L. S. Rallidis, C. B. Granger, A. Rasheed, M. Samuel, S. H. Shah, J. Sinisalo, K. E. Stirrups, S. Trompet, L. Wang, K. S. Zaman, D. Ardissino, E. Boerwinkle, D. Gu, I. B. Borecki, E. P. Bottinger, J. E. Buring, J. C. Chambers, R. Collins, L. A. Cupples, J. Danesh, I. Demuth, R. Elosua, S. E. Epstein, V. Gudnason, T. Esko, M. F. Feitosa, A. S. Hall, A. Hamsten, T. B. Harris, S. L. Hazen, C. Hengstenberg, L. Zeng, A. Hofman, E. Ingelsson, C. Iribarren, J. W. Jukema, P. J. Karhunen, B. -.J. Kim, J. S. Kooner, I. J. Kullo, T. Lehtimäki, R. J. F. Loos, A. Dehghan, O. Melander, A. Metspalu, W. März, C. N. Palmer, M. Perola, T. Quertermous, D. J. Rader, P. M. Ridker, S. Ripatti, R. Roberts, M. Alver, V. Salomaa, D. K. Sanghera, S. M. Schwartz, U. Seedorf, A. F. Stewart, D. J. Stott, J. Thiery, P. A. Zalloua, C. J. O'Donnell, M. P. Reilly, S. M. Armasu, T. L. Assimes, J. R. Thompson, J. Erdmann, R. Clarke, H. Watkins, S. Kathiresan, R. McPherson, P. Deloukas, H. Schunkert, N. J. Samani, K. Auro, M. Farrall, CARDIoGRAMplusC4D Consortium, A. Bjonnes, D. I. Chasman, S. Chen, I. Ford, N. Franceschini, C. Gieger, C. Grace, S. Gustafsson, S.-J. Hwang, Y. K. Kim, M. E. Kleber, K. W. Lau, X. Lu, Y. Lu, L.-P. Lyytikäinen, E. Mihailov, A. C. Morrison, N. Pervjakova, L. Qu, L. M. Rose, E. Salfati, R. Saxena, M. Scholz, A. V. Smith, E. Tikkanen, A. Uitterlinden, X. Yang, W. Zhang, W. Zhao, M. de Andrade, P. S. de Vries
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.

History

Citation

Nature Genetics, 2015, 47 (10), pp. 1121-1130

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences

Version

AM (Accepted Manuscript)

Published in

Nature Genetics

Publisher

Nature Publishing Group

issn

1061-4036

eissn

1546-1718

Acceptance date

14/08/2015

Copyright date

2015

Available date

23/08/2017

Publisher version

http://www.nature.com/ng/journal/v47/n10/full/ng.3396.html?foxtrotcallback=true

Language

en