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Area of Science:

  • Genetics and Cardiovascular Health
  • Metabolic Syndrome Research
  • Personalized Medicine Approaches

Background:

  • Dyslipidemia, characterized by triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels, is a major contributor to cardiovascular disease (CVD).
  • Genetic predisposition plays a significant role in lipid levels, but its interaction with lifestyle factors requires further population-based investigation.

Purpose of the Study:

  • To investigate the associations between weighted polygenic risk scores (wPRS) for TG and HDL-C, lifestyle, and metabolic factors with lipid traits and CVD risk.
  • To explore gene-environment interactions in the context of dyslipidemia and cardiovascular outcomes.

Main Methods:

  • A cross-sectional study analyzing genotype, metabolic, and lifestyle data from 5584 Israeli adults.
  • Construction of individual wPRS for TG and HDL-C using SNPs.
  • Gene-environment associations evaluated by stratifying participants based on high (≥90th percentile) vs. lower (<90th percentile) wPRS.

Main Results:

  • High wPRS for TG and HDL-C were linked to unfavorable lipid profiles and elevated TG/HDL-C ratios.
  • Individuals with high wPRSHDL had substantially higher odds of CVD (97-fold for males, 10-fold for females).
  • Combined high wPRSHDL and wPRSTG increased CVD odds by 44-fold. Obesity and elevated HbA1c exacerbated lipid abnormalities, while moderate wine and coffee intake showed protective effects, especially in high wPRS groups.

Conclusions:

  • Genetic risk stratification, combined with lifestyle and metabolic factors, can identify individuals at high risk for dyslipidemia and CVD.
  • Personalized prevention strategies tailored to genetic predisposition and modifiable lifestyle factors hold promise for mitigating cardiovascular risk.