Influence of lifestyle risk factors and genetic predisposition on metabolic syndrome risk in Korean adults

Metabolic syndrome (MetS) is a major risk factor for cardiovascular and chronic diseases. This study evaluated how genetic predisposition and lifestyle factors contribute to MetS risk. We analysed data from 4,987 Koreans aged ≥ 40 years with at least one ASCVD risk factor (2014-2017). A polygenic risk score for metabolic disease (PRS_MetS) using eight metabolic phenotypes was used to categorise participants into high and low PRS_MetS groups (top 7% vs. bottom 93%). Lifestyle factors, including obesity, physical activity, smoking, diet, and alcohol consumption, were assessed with a healthy lifestyle score. The associations of PRS_MetS and lifestyle factors with MetS risk were evaluated. High PRS_MetS was associated with a 1.31-fold higher risk of MetS (adjusted odds ratio [aOR], 1.31; 95% confidence interval [CI], 1.03-1.66). MetS prevalence increased stepwise with worsening lifestyle in both low and high PRS_MetS groups. Compared to the 'low PRS_MetS and ideal lifestyle' group, MetS risk was significantly higher in all other lifestyle groups, with the highest risk observed in the 'high PRS_MetS and poor lifestyle' (aOR, 9.35; 95% CI, 4.41-19.83) group. Both genetic predisposition and lifestyle factors significantly influenced MetS risk. Maintaining healthy lifestyle habits mitigates MetS risk, even in individuals with high genetic susceptibility.