Mendelian randomization investigation: Exploring the relationship between phosphatidylinositol levels and hypertrophic cardiomyopathy risk through interleukin-20 receptor subunit alpha expression

This Mendelian randomization study investigated the causal relationship between phosphatidylinositol (PI) levels and hypertrophic cardiomyopathy (HCM) risk, while evaluating the potential mediating role of interleukin-20 receptor subunit alpha (IL-20RA). Leveraging genome-wide association study data from Finnish and European populations, our 2-sample Mendelian randomization analysis revealed a significant inverse association between PI levels and HCM risk (odds ratio [OR] = 0.686, 95% confidence interval [CI]: 0.512–0.921; P = .012), with no evidence of reverse causation. The analysis further demonstrated a positive correlation between PI and IL-20RA levels (OR = 1.090, 95% CI: 1.033–1.149; P = .002), while elevated IL-20RA showed a protective association against HCM (OR = 0.514, 95% CI: 0.302–0.873; P = .014). Mediation analysis indicated that approximately 15.2% of PI’s protective effect was mediated through IL-20RA pathways. These findings suggest PI may mitigate HCM risk partially through IL-20RA-mediated mechanisms, highlighting potential therapeutic targets in lipid-inflammatory pathways for HCM intervention. Further research is needed to validate these observational genetic associations.