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Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia.

Publication ,  Journal Article
Han, Y; Dorajoo, R; Chang, X; Wang, L; Khor, C-C; Sim, X; Cheng, C-Y; Shi, Y; Tham, YC; Zhao, W; Chee, ML; Sabanayagam, C; Chee, ML; Tan, N ...
Published in: Sci Rep
December 20, 2017

Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10-8) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10-10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-7-0.047). Seven pathways (P: 1.10 × 10-5-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

Duke Scholars

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

December 20, 2017

Volume

7

Issue

1

Start / End Page

17921

Location

England

Related Subject Headings

  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Han, Y., Dorajoo, R., Chang, X., Wang, L., Khor, C.-C., Sim, X., … Heng, C.-K. (2017). Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia. Sci Rep, 7(1), 17921. https://doi.org/10.1038/s41598-017-18214-z
Han, Yi, Rajkumar Dorajoo, Xuling Chang, Ling Wang, Chiea-Chuen Khor, Xueling Sim, Ching-Yu Cheng, et al. “Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia.Sci Rep 7, no. 1 (December 20, 2017): 17921. https://doi.org/10.1038/s41598-017-18214-z.
Han, Yi, et al. “Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia.Sci Rep, vol. 7, no. 1, Dec. 2017, p. 17921. Pubmed, doi:10.1038/s41598-017-18214-z.
Han Y, Dorajoo R, Chang X, Wang L, Khor C-C, Sim X, Cheng C-Y, Shi Y, Tham YC, Zhao W, Chee ML, Sabanayagam C, Tan N, Wong TY, Tai E-S, Liu J, Goh DYT, Yuan J-M, Koh W-P, van Dam RM, Low AF, Chan MY-Y, Friedlander Y, Heng C-K. Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia. Sci Rep. 2017 Dec 20;7(1):17921.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

December 20, 2017

Volume

7

Issue

1

Start / End Page

17921

Location

England

Related Subject Headings

  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease