Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways.

PRSs were associated with asthma(-related traits) in a Dutch prospective cohort, with substantially higher predictive power observed for COA than for AOA. Importantly, PRS variants could be epigenomically partitioned into clusters of regulatory variants with different pathophysiological association patterns and effect estimates, which likely represent distinct genetically driven disease pathways. Our findings have potential implications for personalized risk mitigation and treatment strategies.