Bidirectional causal relationship between inflammatory cytokines and endometriosis at different sites

Abstract Objective This study aims to explore the genetic connection between inflammatory cytokines (IC) and endometriosis (EMs) to provide insights for the treatment of EMs. Methods Data from two genome-wide association studies (GWAS) on IC and EMs were analyzed for single nucleotide polymorphisms (SNPs). Both forward and reverse Mendelian randomization (MR) analyses were conducted using inverse variance weighting. In the forward MR analysis, IC-related SNPs were used as instrumental variables with EMs as the outcome. Conversely, in the reverse MR analysis, SNPs associated with EMs were used as instrumental variables with IC as the outcome. Analyses were conducted using the TwoSampleMR package in R. Results The forward MR analysis revealed no significant genetic correlation between 51 ICs and EMs (P > 0.05). The reverse MR analysis, however, revealed a significant genetic correlation between EMs and one type of IC (P 0.05). Notably, specific inflammatory factors varied among different EMs sites (P < 0.05). Conclusion Although ICs do not have a genetic influence on EMs, variations in inflammatory factors are observed in EMs patients, especially across different EMs sites. These findings suggest unique inflammatory responses at specific EMs sites.