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We conducted a cross-biobank genome-wide association study of recurrent UTIs in 1,860,836 individuals (213,869 cases and 1,646,967 controls). We identified 36 genetic susceptibility loci and performed tissue-based multi-omic mapping to prioritize candidate causal genes. UTI risk alleles preferentially modulated epithelial gene expression in kidney and bladder, converging on urinary epithelia structure and function.\n                  <jats:italic>PSCA<\/jats:italic>\n                  , encoding a secreted epithelial surface protein, emerged as the strongest candidate under genetic control; the gene product is constitutively secreted into the urine from kidney papilla and bladder epithelia, binds uropathogenic\n                  <jats:italic>E. coli<\/jats:italic>\n                  , and inhibits bacterial growth\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Our findings define the polygenic architecture of UTIs and highlight the critical role of uroepithelial surface defenses, providing a new framework for host-directed, non-antibiotic interventions.\n                <\/jats:p>","DOI":"10.64898\/2026.07.07.26357417","type":"posted-content","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T21:40:11Z","timestamp":1783806011000},"source":"Crossref","is-referenced-by-count":0,"title":["Inherited Susceptibility to Urinary Tract Infections from Kidney Papilla to Bladder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0344-2069","authenticated-orcid":false,"given":"Katherine","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University; New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atlas","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University; 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