Effects of Physical Activity on the Incidence of Stroke with Polygenic Risk Score

PURPOSE: Stroke is influenced by multiple risk factors, including genetic factors summarized by polygenic risk scores (PRS) derived from single nucleotide polymorphisms (SNPs). Physical activity is an important modifiable factor that reduces stroke risk. This study examined the association between physical activity and stroke incidence across different PRS levels.METHODS: Through genome-wide association study (GWAS) analysis, SNPs with high frequency in stroke patients were classified. The presence and amount of physical activity were assessed based on the weekly physical activity reported in the epidemiological survey data. All participants were classified into three groups based on PRS levels. Logistic regression analysis was performed to evaluate the association between physical activity and stroke incidence according to PRS levels.RESULTS: Through GWAS (p<1×10−5), 28 SNPs were identified in the stroke patients for calculating PRS. The PRS was calculated using 11 SNPs derived from GWAS through LD-pruning. Each one-standard deviation increase in PRS was associated with an approximately 2.5-fold increased risk of stroke (OR=2.54, p<.0001). Each one-minute increase in physical activity was associated with an approximately 0.3% decrease in stroke risk (OR=0.997, p=.0214). No significant interaction effects were observed between physical activity and PRS levels in relation to stroke incidence (middle PRS×physical activity: OR=0.998, p=.490; high PRS×physical activity: OR=1.00, p=.969).CONCLUSIONS: This study examined differences in stroke incidence associated with physical activity across PRS levels. Although no significant interaction was observed, the protective effect of physical activity on stroke risk was consistently maintained across PRS levels.