Polygenic Score Approach to Predicting Risk of Metabolic Syndrome

Metabolic syndrome (MetS) is a complex condition linking obesity, diabetes, and hypertension, representing a major challenge in clinical care. Its rising global prevalence, driven by urbanization, sedentary lifestyles, and dietary changes, underscores the need for effective management. This study aims to explore the genetic mechanisms behind MetS, including adiposity, inflammation, neurotransmitters, and β-cell function, to develop a prognostic tool for MetS risk.

We genotyped 40 genetic variants across these pathways in 279 MetS patients and 397 healthy individuals. Using logistic regression, we evaluated the prognostic capability of a polygenic score model for MetS risk, both independently and with other factors like sex and age.

Logistic regression analysis identified 18 genetic variants significantly associated with MetS. The optimal predictive model used polygenic scores calculated with weights assigned to the 18 loci (AUC 82.5%, 95% CI 79.4-85.6%), with age and sex providing a minimal, non-significant improvement (AUC 83.3%, 95% CI 80.2-86.3%). The addition of the polygenic score significantly improved net reclassification (NRI = 1.03%, p = 3.42 × 10^-50). Including all 40 variants did not enhance prediction (NRI = -0.11, p = 0.507).

Polygenic scores could aid in predicting MetS risk and health outcomes, emphasizing the need for diagnostic tools tailored to specific populations. Additional research is warranted to corroborate these conclusions and explore the molecular mechanisms of MetS.