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Large-scale association analysis identifies new risk loci for coronary artery disease.

Publication ,  Journal Article
CARDIoGRAMplusC4D Consortium, ; Deloukas, P; Kanoni, S; Willenborg, C; Farrall, M; Assimes, TL; Thompson, JR; Ingelsson, E; Saleheen, D; Esko, T ...
Published in: Nat Genet
January 2013

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

January 2013

Volume

45

Issue

1

Start / End Page

25 / 33

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Regulatory Networks
 

Citation

APA
Chicago
ICMJE
MLA
NLM
CARDIoGRAMplusC4D Consortium, ., Deloukas, P., Kanoni, S., Willenborg, C., Farrall, M., Assimes, T. L., … Samani, N. J. (2013). Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet, 45(1), 25–33. https://doi.org/10.1038/ng.2480
CARDIoGRAMplusC4D Consortium, Nilesh J., Panos Deloukas, Stavroula Kanoni, Christina Willenborg, Martin Farrall, Themistocles L. Assimes, John R. Thompson, et al. “Large-scale association analysis identifies new risk loci for coronary artery disease.Nat Genet 45, no. 1 (January 2013): 25–33. https://doi.org/10.1038/ng.2480.
CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013 Jan;45(1):25–33.
CARDIoGRAMplusC4D Consortium, Nilesh J., et al. “Large-scale association analysis identifies new risk loci for coronary artery disease.Nat Genet, vol. 45, no. 1, Jan. 2013, pp. 25–33. Pubmed, doi:10.1038/ng.2480.
CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, Stirrups K, König IR, Cazier J-B, Johansson A, Hall AS, Lee J-Y, Willer CJ, Chambers JC, Esko T, Folkersen L, Goel A, Grundberg E, Havulinna AS, Ho WK, Hopewell JC, Eriksson N, Kleber ME, Kristiansson K, Lundmark P, Lyytikäinen L-P, Rafelt S, Shungin D, Strawbridge RJ, Thorleifsson G, Tikkanen E, Van Zuydam N, Voight BF, Waite LL, Zhang W, Ziegler A, Absher D, Altshuler D, Balmforth AJ, Barroso I, Braund PS, Burgdorf C, Claudi-Boehm S, Cox D, Dimitriou M, Do R, DIAGRAM Consortium, CARDIOGENICS Consortium, Doney ASF, El Mokhtari N, Eriksson P, Fischer K, Fontanillas P, Franco-Cereceda A, Gigante B, Groop L, Gustafsson S, Hager J, Hallmans G, Han B-G, Hunt SE, Kang HM, Illig T, Kessler T, Knowles JW, Kolovou G, Kuusisto J, Langenberg C, Langford C, Leander K, Lokki M-L, Lundmark A, McCarthy MI, Meisinger C, Melander O, Mihailov E, Maouche S, Morris AD, Müller-Nurasyid M, MuTHER Consortium, Nikus K, Peden JF, Rayner NW, Rasheed A, Rosinger S, Rubin D, Rumpf MP, Schäfer A, Sivananthan M, Song C, Stewart AFR, Tan S-T, Thorgeirsson G, van der Schoot CE, Wagner PJ, Wellcome Trust Case Control Consortium, Wells GA, Wild PS, Yang T-P, Amouyel P, Arveiler D, Basart H, Boehnke M, Boerwinkle E, Brambilla P, Cambien F, Cupples AL, de Faire U, Dehghan A, Diemert P, Epstein SE, Evans A, Ferrario MM, Ferrières J, Gauguier D, Go AS, Goodall AH, Gudnason V, Hazen SL, Holm H, Iribarren C, Jang Y, Kähönen M, Kee F, Kim H-S, Klopp N, Koenig W, Kratzer W, Kuulasmaa K, Laakso M, Laaksonen R, Lind L, Ouwehand WH, Parish S, Park JE, Pedersen NL, Peters A, Quertermous T, Rader DJ, Salomaa V, Schadt E, Shah SH, Sinisalo J, Stark K, Stefansson K, Trégouët D-A, Virtamo J, Wallentin L, Wareham N, Zimmermann ME, Nieminen MS, Hengstenberg C, Sandhu MS, Pastinen T, Syvänen A-C, Hovingh GK, Dedoussis G, Franks PW, Lehtimäki T, Metspalu A, Zalloua PA, Siegbahn A, Schreiber S, Ripatti S, Blankenberg SS, Perola M, Clarke R, Boehm BO, O’Donnell C, Reilly MP, März W, Collins R, Kathiresan S, Hamsten A, Kooner JS, Thorsteinsdottir U, Danesh J, Palmer CNA, Roberts R, Watkins H, Schunkert H, Samani NJ. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013 Jan;45(1):25–33.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

January 2013

Volume

45

Issue

1

Start / End Page

25 / 33

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Regulatory Networks