ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026
Gut-reproduction axis: genome-wide pleiotropic and prospective evidence linking inflammatory bowel disease with gynecological disorders.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveWe aimed to explore shared genetic architectures and potential causal associations between inflammatory bowel disease (IBD) and gynecological diseases, including ovarian cysts (OC), pelvic inflammatory disease (PID), and endometriosis (EMs), and to evaluate whether the findings are consistent with a gut-reproductive connection.
methodsWe used genome-wide association study (GWAS) data to assess genetic correlation between IBD and gynecological diseases. Cross-trait pleiotropic loci and genes were identified using PLACO, colocalization, and functional annotation analyses. Stratified LDSC and HyPrColoc were applied to explore immune-related enrichment and colocalized immune traits. Mendelian randomization (MR) was used to assess bidirectional causal effects, and UK Biobank cohort data were analyzed using Cox proportional hazards models.
resultsGenetic correlation analyses supported shared genetic architecture between IBD and gynecological diseases. Pleiotropy and colocalization analyses highlighted representative loci including 6q22.33, 9q34, 1q21.3, 16q12.1, 6q27, and 1q32.1, with enrichment of immune-related pathways such as IL-23 and JAK-STAT signaling, particularly in the colon, small intestine, and spleen. Colocalization signals involving Ruminococcus gauvreauii suggested overlap with microbial abundance traits. MR analyses provided the most consistent evidence for directional associations from IBD and CD to PID, whereas UK Biobank analyses supported broader bidirectional associations, particularly for OC and PID.
conclusionThis study identifies shared genetic loci, immune-related pathways, and complementary causal and observational associations between IBD and gynecological conditions. These findings support the gut-reproductive axis as a conceptual framework for future mechanistic investigation.
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