Interplay between Polygenic Variants Related Immune Response and Lifestyle Factors Mitigate the Chances of Stroke in a Genome-Wide Association Study.

We aimed to investigate the intricate interplay between genetic predisposition and lifestyle factors on stroke. We conducted a comprehensive genome-wide association study(GWAS) to identify the genetic variants linked to stroke in the participants who experienced a stroke event(cases; n=672) and those with no stroke history(non-stroke; n=58,029) in a large hospital-based cohort. Using generalized multifactor dimensionality reduction, we identified genetic variants with interactive effects and constructed polygenic risk scores(PRS) by summing up the risk alleles from the genetic variants. Food intake was measured with a validated semi-quantitative food frequency questionnaire. No significant differences in stroke incidence were seen in demographic variables between the two groups. Among the metabolic indicators, only serum triglyceride levels were higher in males with stroke than those without stroke. The daily nutrient intake, dietary inflammation index, glycemic index, dietary patterns, alcohol consumption, exercise, and smoking did not display associations with the odds ratio for stroke. The stroke-linked genetic variants were related to the interleukin-18( IL-18 ) pathway. After accounting for covariates, the PRS derived from the 5-, 6-, and 7-single nucleotide polymorphism(SNP) models were positively associated with stroke chance with 2.5-, 2.9-, and 2.8-fold. Furthermore, interactions between genetic predisposition and dietary components, including energy, carbohydrates, n-3 fatty acids, and branched-chain amino acids(BCAAs), that affected odds ratios for stroke were observed. A high intake of energy, carbohydrates, and BCAAs and a low intake of n-3 fatty acids were positively associated with the chances of stroke occurrence. In conclusion, understanding the interaction between genetic variants and lifestyle factors can assist in developing stroke prevention and management strategies.