Moreover, based on the matched data, only CRP, neutrophils, and leukocytes significantly mediated the prospective association between frailty and depression incidence (Bonferroni-corrected two-side P < 0.05/9 for nine tests), with the proportion of mediated variance being 3.18% (95% CI [1.03%, 5.41%], P = 2.80 × 10−3), 2.34% ([1.00%, 3.69%], P = 8.00 × 10−4), and 2.34% ([1.09%, 3.69%], P = 2.00 × 10−4), respectively (Fig. 4C, Supplementary Table 11). This evidence concerns the gene CRP and depressive disorder.