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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nikpay, M; Goel, A; Won, H-H; Hall, LM; Willenborg, C; Kanoni, S; Saleheen, D; Kyriakou, T; Nelson, CP; Hopewell, JC; Webb, TR; Zeng, L; Dehghan, A; Alver, M; Armasu, SM; Auro, K; Bjonnes, A; Chasman, DI; Chen, S; Ford, I; Franceschini, N; Gieger, C; Grace, C; Gustafsson, S; Huang, J; Hwang, S-J; Kim, YK; Kleber, ME; Lau, KW; Lu, X; Lu, Y; Lyytikäinen, L-P; 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, B-G; Huang, J; Jalilzadeh, S; Kessler, T; König, IR; Lannfelt, L; Lieb, W; Lind, L; Lindgren, CM; Lokki, M-L; Magnusson, PK; Mallick, NH; Mehra, N; Meitinger, T; Memon, F-U-R; Morris, AP; Nieminen, MS; Pedersen, NL; Peters, A; Rallidis, LS; Rasheed, A; Samuel, M; Shah, SH; Sinisalo, J; Stirrups, KE; Trompet, S; Wang, L; Zaman, KS; Ardissino, D; Boerwinkle, E; Borecki, IB; Bottinger, EP; Buring, JE; Chambers, JC; Collins, R; Cupples, LA; Danesh, J; Demuth, I; Elosua, R; Epstein, SE; Esko, T; Feitosa, MF; Franco, OH; Franzosi, MG; Granger, CB; Gu, D; Gudnason, V; Hall, AS; Hamsten, A; Harris, TB; Hazen, SL; Hengstenberg, C; Hofman, A; Ingelsson, E; Iribarren, C; Jukema, JW; Karhunen, PJ; Kim, B-J; 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

Published Date

  • October 2015

Published In

Volume / Issue

  • 47 / 10

Start / End Page

  • 1121 - 1130

PubMed ID

  • 26343387

Pubmed Central ID

  • 26343387

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.3396

Language

  • eng