Mendelian randomization investigation: Exploring the relationship between phosphatidylinositol levels and...

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.