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

Publication ,  Journal Article
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 ...
Published in: Nat Genet
October 2015

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2015

Volume

47

Issue

10

Start / End Page

1121 / 1130

Location

United States

Related Subject Headings

  • Phenotype
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Developmental Biology
  • Coronary Artery Disease
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3001 Agricultural biotechnology
  • 11 Medical and Health Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nikpay, M., Goel, A., Won, H.-H., Hall, L. M., Willenborg, C., Kanoni, S., … Farrall, M. (2015). A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet, 47(10), 1121–1130. https://doi.org/10.1038/ng.3396
Nikpay, Majid, Anuj Goel, Hong-Hee Won, Leanne M. Hall, Christina Willenborg, Stavroula Kanoni, Danish Saleheen, et al. “A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.Nat Genet 47, no. 10 (October 2015): 1121–30. https://doi.org/10.1038/ng.3396.
Nikpay M, Goel A, Won H-H, Hall LM, Willenborg C, Kanoni S, et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015 Oct;47(10):1121–30.
Nikpay, Majid, et al. “A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.Nat Genet, vol. 47, no. 10, Oct. 2015, pp. 1121–30. Pubmed, doi:10.1038/ng.3396.
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, 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. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015 Oct;47(10):1121–1130.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2015

Volume

47

Issue

10

Start / End Page

1121 / 1130

Location

United States

Related Subject Headings

  • Phenotype
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Developmental Biology
  • Coronary Artery Disease
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3001 Agricultural biotechnology
  • 11 Medical and Health Sciences