Estimation of Peptic ulcer risk through Mendelian randomization analyses using genetically predicted circulating levels of cytokines

Abstract

Abstract Background The association of some inflammatory cytokines such as CRP, IL-1, and TNFα with peptic ulcer has been reported. To investigate the causal relationship between 41 inflammatory cytokines and peptic ulcers, a Mendelian randomization (MR) analysis was conducted. Methods: Two-sample MR was conducted using data available on genetic variation in peptic ulcer from a comprehensive genome-wide association study (GWAS) that included 130 individuals of European ancestry with peptic ulcer and 189,695 control participants. Additionally, data on inflammatory cytokines were obtained from a pooled GWAS comprising 8,293 healthy individuals. The causal relationship between exposure and outcome was explored primarily using an inverse variance weighting approach. Furthermore, several sensitivity analysis techniques, such as MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were employed to strengthen the robustness of the final findings. Results: The acquired data implied that platelet-derived growth factor-BB (PDGF_BB), stromal cell-derived factor-1α (SDF_1A), and macrophage inflammatory protein 1-a (MIP_1A) may be associated with the risk of peptic ulcer ([ORIVW: 4.148. 95% CI: 1.74-9. 87; P = .0013], MIP_1A [ORIVW: 0.199; 95% CI: 0.067–0.593; P = .0037] SDF_1A [ORIVW: 0.318,0.117–0.866; P = .0249]. Furthermore, the absence of inflammatory factors is considered a consequence of PUD. Conclusion: The present study suggests that PDGF_BB, SDF_1A, and MIP_1A may be factors associated with PUD.