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

Nikpay, Majid; Goel, Anuj; Won, Hong-Hee; Hall, Leanne M.; Willenborg, Christina; Kanoni, Stavroula; Saleheen, Danish; Kyriakou, Theodosios; Nelson, Christopher P. and Hopewell, Jemma C., et al. (2015) In Nature Genetics 47(10). p.1121-1121
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 similar to 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... (More)
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 similar to 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. (Less)
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Nature Genetics
volume
47
issue
10
pages
1121 - 1121
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Nature Publishing Group
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  • wos:000361969900007
  • scopus:84942987885
ISSN
1546-1718
DOI
10.1038/ng.3396
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English
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327d82ec-1f85-4cd1-9cfb-69b27e0c7026 (old id 8221573)
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2015-11-30 14:39:17
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@article{327d82ec-1f85-4cd1-9cfb-69b27e0c7026,
  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 similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) &gt; 0.05) and 2.7 million low-frequency (0.005 &lt; MAF &lt; 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       = {Nikpay, Majid and Goel, Anuj and Won, Hong-Hee and Hall, Leanne M. and Willenborg, Christina and Kanoni, Stavroula and Saleheen, Danish and Kyriakou, Theodosios and Nelson, Christopher P. and Hopewell, Jemma C. and Webb, Thomas R. and Zeng, Lingyao and Dehghan, Abbas and Alver, Maris and Armasu, Sebastian M. and Auro, Kirsi and Bjonnes, Andrew and Chasman, Daniel I. and Chen, Shufeng and Ford, Ian and Franceschini, Nora and Gieger, Christian and Grace, Christopher and Gustafsson, Stefan and Huang, Jie and Hwang, Shih-Jen and Kim, Yun Kyoung and Kleber, Marcus E. and Lau, King Wai and Lu, Xiangfeng and Lu, Yingchang and Lyytikainen, Leo-Pekka and Mihailov, Evelin and Morrison, Alanna C. and Pervjakova, Natalia and Qu, Liming and Rose, Lynda M. and Salfati, Elias and Saxena, Richa and Scholz, Markus and Smith, Albert V. and Tikkanen, Emmi and Uitterlinden, Andre and Yang, Xueli and Zhang, Weihua and Zhao, Wei and de Andrade, Mariza and de Vries, Paul S. and van Zuydam, Natalie R. and Anand, Sonia S. and Bertram, Lars and Beutner, Frank and Dedoussis, George and Frossard, Philippe and Gauguier, Dominique and Goodall, Alison H. and Gottesman, Omri and Haber, Marc and Han, Bok-Ghee and Huang, Jianfeng and Jalilzadeh, Shapour and Kessler, Thorsten and Koenig, Inke R. and Lannfelt, Lars and Lieb, Wolfgang and Lind, Lars and Lindgren, Cecilia M. and Lokki, Marja-Liisa and Magnusson, Patrik K. and Mallick, Nadeem H. and Mehra, Narinder and Meitinger, Thomas and Memon, Fazal-ur-Rehman and Morris, Andrew P. and Nieminen, Markku S. and Pedersen, Nancy L. and Peters, Annette and Rallidis, Loukianos S. and Rasheed, Asif and Samuel, Maria and Shah, Svati H. and Sinisalo, Juha and Stirrups, Kathleen E. and Trompet, Stella and Wang, Laiyuan and Zaman, Khan S. and Ardissino, Diego and Boerwinkle, Eric and Borecki, Ingrid B. and Bottinger, Erwin P. and Buring, Julie E. and Chambers, John C. and Collins, Rory and Cupples, L. Adrienne and Danesh, John and Demuth, Ilja and Elosua, Roberto and Epstein, Stephen E. and Esko, Tonu and Feitosa, Mary F. and Franco, Oscar H. and Franzosi, Maria Grazia and Granger, Christopher B. and Gu, Dongfeng and Gudnason, Vilmundur and Hall, Alistair S. and Hamsten, Anders and Harris, Tamara B. and Hazen, Stanley L. and Hengstenberg, Christian and Hofman, Albert and Ingelsson, Erik and Iribarren, Carlos and Jukema, J. Wouter and Karhunen, Pekka J. and Kim, Bong-Jo and Kooner, Jaspal S. and Kullo, Iftikhar J. and Lehtimaki, Terho and Loos, Ruth J. F. and Melander, Olle and Metspalu, Andres and Maerz, Winfried and Palmer, Colin N. and Perola, Markus and Quertermous, Thomas and Rader, Daniel J. and Ridker, Paul M. and Ripatti, Samuli and Roberts, Robert and Salomaa, Veikko and Sanghera, Dharambir K. and Schwartz, Stephen M. and Seedorf, Udo and Stewart, Alexandre F. and Stott, David J. and Thiery, Joachim and Zalloua, Pierre A. and O'Donnell, Christopher J. and Reilly, Muredach P. and Assimes, Themistocles L. and Thompson, John R. and Erdmann, Jeanette and Clarke, Robert and Watkins, Hugh and Kathiresan, Sekar and McPherson, Ruth and Deloukas, Panos and Schunkert, Heribert and Samani, Nilesh J. and Farrall, Martin},
  issn         = {1546-1718},
  language     = {eng},
  number       = {10},
  pages        = {1121--1121},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease},
  url          = {http://dx.doi.org/10.1038/ng.3396},
  volume       = {47},
  year         = {2015},
}