{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:58:24Z","timestamp":1781643504185,"version":"3.54.5"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Chlamydia trachomatis (Ct)<\/jats:italic> is a bacterium that causes chlamydia, the most diagnosed bacterial sexually transmitted infection (STI) in the world. In the U.S., chlamydia is most prevalent among non-Hispanic African American (AA) individuals, implying substantial racial disparity. Despite prevention and control efforts, reinfection is common, suggesting that some individuals have insufficient protective immunity to <jats:italic>Ct<\/jats:italic>. To better understand the genetically mediated risks of chlamydia reinfection, we sought to identify genetic loci associated with reinfection using a Genome-Wide Association Study (GWAS) approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We performed GWAS in 300 AA women with versus without chlamydia reinfection based on <jats:italic>Ct<\/jats:italic> testing done about 3 months after chlamydia treatment. We conducted logistic regression models to test the additive genetic effect and used Firth regression to confirm the association results. Furthermore, we performed post-GWAS analysis to determine the functional consequences of GWAS hits, including fine-mapping, expression quantitative loci (eQTL) and chromatin interaction analyses, tissue and cell-type expression, and pathway analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GWAS identified 17 suggestive genomic regions of interest. Five genomic regions out of 17 were identified as strongly associated with reinfection, using linkage disequilibrium and fine mapping. The positional mapping, eQTL, and chromatin interactions (CIs) analyses further identified 12 gene targets. Among the 12 gene targets, <jats:italic>CHIT1<\/jats:italic>, <jats:italic>ADORA1<\/jats:italic>, and <jats:italic>CHI3L1<\/jats:italic> in chromosome 1 (chr. 1); <jats:italic>TDRP<\/jats:italic>, <jats:italic>FBXO25<\/jats:italic>, and <jats:italic>SULF1<\/jats:italic> in chr. 8; and the <jats:italic>SOCS6<\/jats:italic> gene in chr. 18, were functionally relevant to reinfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This GWAS study in AA women identified multiple novel genes associated with chlamydia reinfection, including <jats:italic>CHIT1, CHI3L1, ADORA1, ALK, TDRP, FBXO25, LINC01592, SULF1<\/jats:italic>, and <jats:italic>SOCS6<\/jats:italic>, which are involved in the immune response. <jats:italic>CHIT1, ADORA1, CHI3L1, TDRP, FBOXO25<\/jats:italic>, <jats:italic>SULF1<\/jats:italic>, and <jats:italic>SOCS6<\/jats:italic> were identified using CI\/eQTL mapping.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1594317","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:51:44Z","timestamp":1758793904000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome-wide association study of chlamydia reinfection in African American women"],"prefix":"10.3389","volume":"16","author":[{"given":"Hemant K.","family":"Tiwari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Patki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Srinivasasainagendra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep 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