Causal relationship between circulating inflammatory cytokines and the risk of hernia: a bidirectional Mendelian...

Observational studies suggest a link between hernia and inflammatory cytokines, but randomized trials are limited by ethical and cost constraints. In this study, we used bidirectional Mendelian randomization (MR) to investigate the causal relationship between inflammatory cytokines and five types of hernia, aiming to inform preventive and therapeutic strategies.

We selected 41 inflammatory factors and five types of hernia as instrumental variables, using data from the IEU Open GWAS database including individuals of European descent. The primary analysis used the inverse variance weighted method with false discovery rate (FDR) adjustment. Additional MR methods and sensitivity analyses ensured robustness. Reverse MR was used to assess potential reverse causality.

After FDR adjustment, stem cell growth factor beta (SCGFb) was causally associated with diaphragmatic hernia (odds ratio = 0.884, 95% confidence interval: 0.819-0.955). Reverse MR indicated that diaphragmatic hernia may increase interferon gamma-induced protein 10 (IP10) and monokine induced by interferon-gamma (MIG), and ventral hernia may elevate macrophage inflammatory protein-1b (MIP1b). Sensitivity analyses confirmed robustness.

SCGFb may protect against diaphragmatic hernia, and IP10, MIG, and MIP1b are involved in hernia development, suggesting the therapeutic potential of targeting these cytokines. Further studies are needed.