Skip to main content

Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

Publication ,  Journal Article
IBC 50K CAD Consortium,
Published in: PLoS Genet
September 2011

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002260

Location

United States

Related Subject Headings

  • White People
  • Risk
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
IBC 50K CAD Consortium, . (2011). Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet, 7(9), e1002260. https://doi.org/10.1371/journal.pgen.1002260
IBC 50K CAD Consortium, Ralph B. “Large-scale gene-centric analysis identifies novel variants for coronary artery disease.PLoS Genet 7, no. 9 (September 2011): e1002260. https://doi.org/10.1371/journal.pgen.1002260.
IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet. 2011 Sep;7(9):e1002260.
IBC 50K CAD Consortium, Ralph B. “Large-scale gene-centric analysis identifies novel variants for coronary artery disease.PLoS Genet, vol. 7, no. 9, Sept. 2011, p. e1002260. Pubmed, doi:10.1371/journal.pgen.1002260.
IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet. 2011 Sep;7(9):e1002260.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002260

Location

United States

Related Subject Headings

  • White People
  • Risk
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Female