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

TitleA comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsNikpay, 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, YKyoung, Kleber, ME, Lau, KWai, 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, L Cupples, A, Danesh, J, Demuth, I, Elosua, R, Epstein, SE, Esko, T, Feitosa, MF, Franco, OH, Franzosi, MGrazia, Granger, CB, Gu, D, Gudnason, V, Hall, AS, Hamsten, A, Harris, TB, Hazen, SL, Hengstenberg, C, Hofman, A, Ingelsson, E, Iribarren, C, J Jukema, W, Karhunen, PJ, Kim, B-J, Kooner, JS, Kullo, IJ, Lehtimäki, T, Loos, RJF, Melander, O, Metspalu, A, Marz, 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
JournalNat Genet
Volume47
Issue10
Pagination1121-1130
Date Published2015 Oct
ISSN1546-1718
KeywordsCoronary Artery Disease, Genome, Human, Genome-Wide Association Study, Humans, Phenotype
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.
DOI10.1038/ng.3396
Alternate JournalNat. Genet.
PubMed ID26343387
PubMed Central IDPMC4589895
Grant ListRG/08/014/24067 / / British Heart Foundation / United Kingdom
R01 HL127564 / HL / NHLBI NIH HHS / United States
MR/L003120/1 / / Medical Research Council / United Kingdom
RE/13/1/30181 / / British Heart Foundation / United Kingdom
R33 HL120757 / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
FS/14/55/30806 / / British Heart Foundation / United Kingdom
RG/14/5/30893 / / British Heart Foundation / United Kingdom
R01 HL117078 / HL / NHLBI NIH HHS / United States
MR/L01629X/1 / / Medical Research Council / United Kingdom