![]() Shared genetic loci may contribute to risk of both endometriosis and digestive disorders through the involvement of DNA damage, estrogen regulated cell-proliferation and inflammation, and barrier dysfunction. Cross-trait meta-analysis and colocalization along with comprehensive functional annotation confirmed two shared genetic loci ( FN1, TACSTD2) for endometriosis with IBS and twelve loci ( ETAA1, HOXC4, RERG, SEMA3F, SPAG16, HIST1H2BC, RAB5B, CCKBR and PDE4B) with GORD and PUD. Mendelian randomization analysis identified a causal effect of the GPM phenotype on endometriosis and a bidirectional causal association between endometriosis and IBS. Here, using large-scale multifaceted data including observational, genetic, and pharmaceutical datasets, we report a positive phenotypic and genetic association of endometriosis with peptic ulcer disease (PUD), gastro-oesophageal reflux disease (GORD), a combined GORD/PUD Medicated (GPM) phenotype and irritable bowel syndrome (IBS), but not with inflammatory bowel disease (IBD). ![]() In clinical practice, the co-existence of endometriosis and gastrointestinal symptoms is often observed however, the factors driving this link remain largely unknown. ![]()
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