IDDF2023-ABS-0017 Endometriosis increases the risk of inflammatory bowel disease: a mendelian randomization study

Background Previous studies have suggested some relationship between endometriosis (EMS) and inflammatory bowel disease (IBD). However, the causal relationship between the two diseases remains unknown. Our aim was to investigate whether EMS acted as a risk factor for the occurrence of IBD, using a two-sample Mendelian randomization (MR). Methods Genetic variants for investigating the causal effects of EMS (Ncase=12,056, Ncontrol=94,394) on IBD (Ncase=12,882, Ncontrol=21,770) were screened from the genome-wide association study (GWAS) summary statistics of European descent (GWAS P<5*10-8). The MR was performed using different methods: weighted median, inverse-variance weighting (IVW), and MR Egger. The Cochran’s Q test was utilized to evaluate heterogeneity. The MR-Egger intercept test, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out were used to assess horizontal pleiotropy. The MR Steiger test was used to judge ‘correct causal direction’ (IDDF2023-ABS-0017 Figure 1A. The MR illustration) (IDDF2023-ABS-0017 Figure 1B. Workflow of the study design). Results EMS was associated with a 12.8% increase in the risk of IBD (PIVW=0.003). Analyses on the main subtypes of IBD (UC and CD) revealed that EMS was suggestively associated with CD (PIVW=0.04), but the statistical significance was lost after Bonferroni-adjusted adjustment (level of significance P<0.017). We evaluated the IBD risk in the early (I/II) and late (III/IV) American Society for Reproductive Medicine (ASRM) stages of EMS patients, only late-stage patients were significantly associated with increased risks of IBD (PIVW=0.014). There was no significant association between late-stage EMS and UC or CD. We further analyzed the causal estimates from different subtypes of EMS on IBD, including EMS of the ovary, pelvic peritoneum, uterus, rectovaginal septum and vagina, and occurring infertility. Significantly increased IBD risks were found only in ovarian EMS (PIVW=0.005) (IDDF2023-ABS-0017 Figure 2. Causal estimates of EMS on IBD). Conclusions Our study identified EMS as a risk factor for IBD occurrence, especially in late-stage EMS patients. Patients with EMS need to be called attention to avoid exposure to other risk factors of IBD.