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Though IC\/BPS can be hereditary, little is known of its genetic etiology. Using the eMERGE data, we confirmed known phenotypic associations such as gastroesophageal reflux disease and irritable bowel syndrome and detected new associations, including osteoarthrosis\/osteoarthritis and Barrett\u2019s esophagus. An exome wide ultra-rare variants analysis in 348 IC\/BPS and 11,981 controls extended the previously reported association with\n                  <jats:italic>ATP2C1<\/jats:italic>\n                  and\n                  <jats:italic>ATP2A2,<\/jats:italic>\n                  implicated in Mendelian desquamating skin disorders, but did not provide evidence for other previously proposed pathogenic pathways such as bladder development, nociception or inflammation. Pathway analysis detected new associations with \u201canaphase-promoting complex-dependent catabolic process\u201d, the \u201cregulation of MAPK cascade\u201d and \u201cintegrin binding\u201d. These findings suggest perturbations in biological networks for epithelial integrity and cell cycle progression in IC\/BPS pathogenesis, and provide a roadmap for its future investigation.\n                <\/jats:p>","DOI":"10.1101\/2025.02.16.25322147","type":"posted-content","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:50:41Z","timestamp":1739926241000},"source":"Crossref","is-referenced-by-count":0,"title":["Interstitial Cystitis: a phenotype and rare variant exome sequencing study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-4182","authenticated-orcid":false,"given":"Joshua E.","family":"Motelow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayan","family":"Malakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarath Babu","family":"Krishna 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