IRF1 and acute respiratory distress syndrome: Furthermore, mediation analysis revealed that HLA-F mediated the protective effects of IRF1 on acute physiology severity (βindirect = −4.50, 95% CI: −7.31 to −1.69, 98.9% mediated, P = 0.002), ARDS risk (βindirect = −0.42, 95% CI: −0.69 to −0.15, 77.1% mediated, P = 0.002), and both 28-day (βindirect = −0.53, 95% CI: −0.99 to −0.08, 73.8% mediated, P = 0.022) and 60-day survival (βindirect = −0.47, 95% CI: −0.88 to −0.07, 77.8% mediated, P = 0.022; Fig. 3G and 3H), which implies a potential regulatory pathway.