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[Age-Dependent Approach to Search for Genetic Variants Associated with Myocardial Infarction].

G J Osmak1,2,3, A R Sidko1, I S Kiselev1,2

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Summary

This study analyzed genetic factors influencing myocardial infarction (MI) onset age. Specific gene variants were linked to earlier disease development, suggesting a more promising age-dependent approach over traditional case-control methods for understanding genetic susceptibility.

Keywords:
age-dependent diseasesmachine learningmyocardial infarctionsingle nucleotide polymorphismssurvival analysis

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Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Gerontology

Background:

  • Myocardial infarction (MI) is a leading cause of death associated with cardiovascular aging.
  • Traditional case-control studies for genetic susceptibility face challenges in defining healthy control groups.
  • Previous research identified potential gene associations with MI using a case-control design.

Purpose of the Study:

  • To analyze survival functions for carriers of polymorphic variants in 18 genes previously associated with MI.
  • To estimate the shift in MI onset age based on individual genomic variations.
  • To compare the age-dependent approach with the case-control method for studying genetic susceptibility to MI.

Main Methods:

  • Survival function analysis was performed on carriers of alternative polymorphic variants of 18 genes.
  • The age of MI onset was estimated in relation to specific genetic variations.
  • Results were compared with previous findings from a case-control study on the same sample.

Main Results:

  • Five risk variants (rs2430561*A of IFNG, rs1799889*5 of PAI-1, rs1800896*GG of IL10, rs1800471*C of TGFB1, and rs11614913*TT of MIR196A2) were significantly associated with MI age.
  • Carriers of these risk variants experienced MI onset 3-6 years earlier than carriers of alternative variants.
  • Estimates from the age-dependent approach largely disagreed with the case-control approach findings.

Conclusions:

  • The age-dependent survival function analysis identified specific genetic variants that accelerate MI onset.
  • The age-dependent approach appears more promising than the case-control design due to fewer unverifiable assumptions.
  • This method offers a potentially more robust way to study the genetic basis of age-dependent diseases like MI.