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Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary

Qiwen Zheng1, Yan Zhang2, Jie Jiang2

  • 1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Frontiers in Genetics
|April 25, 2020
PubMed

Insights

This study identified genetic variations linked to acute coronary syndromes (ACS) in Chinese Han individuals. A promising variant, rs10409124 at STRN4, showed potential impact across populations, with four genes associated with ACS.

Area of Science:

  • Genetics
  • Cardiovascular Disease Research
  • Population Genetics

Background:

  • Genome-wide association studies (GWAS) have identified over 150 susceptibility loci for coronary artery disease (CAD).
  • A significant portion of CAD heritability remains unexplained, necessitating further investigation into genetic factors.
  • Acute coronary syndromes (ACS) represent a critical manifestation of CAD, requiring deeper understanding of its genetic underpinnings.

Purpose of the Study:

  • To identify population-based genetic variations associated with acute coronary syndromes (ACS) in individuals of Chinese Han descent.
  • To enhance statistical power and reduce bias by integrating a risk prediction model into control selection for genetic association analysis.
  • To explore aggregate effects of genetic variants through gene- and pathway-based analyses.

Main Methods:

  • Exome-wide association analysis was conducted on 1,669 ACS patients and 1,935 healthy controls.
  • Promising genetic variants were validated using an existing in silico dataset.
  • Gene-based and pathway-based analyses were performed to assess the collective impact of variants within genes and biological pathways.

Main Results:

  • No single association signal reached genome-wide significance after Bonferroni correction across all analyses.
  • A specific variant, rs10409124 in the STRN4 gene, demonstrated potential association with ACS in both European and East Asian populations.
  • Gene-based analysis identified four candidate genes (ANXA7, ZNF655, ZNF347, ZNF750) associated with ACS, with ZNF655 replicated in an independent dataset.
  • Pathway analysis suggested the involvement of 32 potential pathways in ACS pathogenesis.

Conclusions:

  • The study identified several candidate genes and pathways potentially involved in the pathogenesis of ACS.
  • The variant rs10409124 at STRN4 warrants further investigation for its role in ACS across diverse populations.
  • The identified genes and pathways represent potential targets for future therapeutic strategies in managing ACS.

Keywords:
acute coronary syndromecontrol selection strategyexome-wide association studygene-based analysispathway-based analysisrisk prediction tool

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