Exploring causal relationships between circulating inflammatory proteins and superficial thrombophlebitis: A...

This study explores the potential causal relationship between circulating inflammatory proteins and superficial thrombophlebitis (STP) using Mendelian randomization (MR). We utilized data on 91 circulating inflammatory proteins from publicly available genome-wide association studies and STP data from the FinnGen consortium's R11 release. The primary analysis method was inverse variance-weighted analysis, complemented by MR-Egger regression and weighted median methods for validation. Additionally, sensitivity analyses and reverse MR tests were conducted to assess the reliability of the results. In the inverse-variance weighted analysis, we observed nominal positive associations between circulating inflammatory proteins, including neurotrophin-3 (NT-3) (OR = 1.132, 95%CI: 1.024-1.252, P = .016), osteoprotegerin (OR = 1.120, 95%CI: 1.013-1.238, P = .027), and vascular endothelial growth factor A (OR = 1.068, 95%CI: 1.008-1.132, P = .027), and the risk of STP (all raw P < .05). Conversely, interleukin-12 subunit beta (OR = 0.917, 95%CI: 0.858-0.980, P = .011) and interleukin-8 (OR = 0.905, 95%CI: 0.824-0.993, P = .035) showed nominal inverse associations with STP risk. However, none of these associations remained statistically significant after Bonferroni or Benjamini-Hochberg FDR correction for multiple testing. Sensitivity analyses showed no significant pleiotropy or heterogeneity, and the effect directions were consistent across complementary MR methods. This hypothesis-generating MR study identified nominal suggestive associations between 5 circulating inflammatory proteins (neurotrophin-3, osteoprotegerin, vascular endothelial growth factor, interleukin-12 subunit beta, and interleukin-8) and STP risk, though none survived correction for multiple testing. These findings provide candidate inflammatory proteins for future validation and underscore the potential role of inflammation in STP pathogenesis.