{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:30:35Z","timestamp":1791898235810,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000964","name":"Arthritis National Research Foundation","doi-asserted-by":"publisher","award":["128808"],"award-info":[{"award-number":["128808"]}],"id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","award":["1520395"],"award-info":[{"award-number":["1520395"]}],"id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Objective<\/jats:title>\n Clonal hematopoiesis (CH), defined by acquired driver mutations in hematopoietic stem cells, is associated with many inflammatory diseases of aging. We investigated whether CH and its subtypes, CH of indeterminate potential (CHIP) and mosaic chromosomal alteration (mCA), are associated with incident rheumatoid arthritis (RA) and whether complement modifies these associations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n CHIP was detected in NIH All of Us, Vanderbilt BioVU, and UK Biobank; mCA was detected in UK Biobank. A harmonized, high\u2010specificity phenotyping algorithm was applied across biobanks to identify participants with seropositive and seronegative RA (SPRA and SNRA). Age\u2010scale survival models assessed the effect of CH on risk of incident RA. Effect modification was tested with interaction models with genetically predicted complement protein levels.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 612,989 participants, 30,840 had CHIP, 1,535 had incident SPRA, and 1,090 had incident SNRA. CHIP was associated with an increased risk of incident SPRA (pooled hazard ratio [HR] 1.26; confidence interval [CI] 1.03\u20131.52;\n P<\/jats:italic>\n \u00a0=\u00a02.3\u2009\u00d7\u200910\n \u22122<\/jats:sup>\n ), driven primarily by\n DNMT3A<\/jats:italic>\n \u2010mutated CHIP and late\u2010onset RA (HR 1.45; CI 1.13\u20131.96;\n P<\/jats:italic>\n \u00a0=\u00a03.6\u2009\u00d7\u200910\n \u22123<\/jats:sup>\n ) but not SNRA. Autosomal mCA and mosaic loss of chromosome Y (mLOY) were associated with an increased risk of incident SPRA (HR 2.12 and 2.85; CI 1.18\u20133.8 and 1.57\u20135.19;\n P<\/jats:italic>\n \u00a0=\u00a01.2\u2009\u00d7\u200910\n \u22122<\/jats:sup>\n and 6.1\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ) but not SNRA. Higher genetically predicted levels of C1r and C1s attenuated the CHIP\u2013SPRA association.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Age\u2010related CH, including\n DNMT3A<\/jats:italic>\n \u2010CHIP, autosomal mCA, and mLOY, are risk factors for incident SPRA but not SNRA, supporting a genotype\u2010 and serostatus\u2010specific link between somatic mutation and RA, with the classical complement pathway as a potential modifier.\n <\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70133","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:01:44Z","timestamp":1773828104000},"page":"2063-2073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of Clonal Hematopoiesis With Incident, Late\u2010Onset, Seropositive Rheumatoid Arthritis"],"prefix":"10.1002","volume":"78","author":[{"given":"Kun","family":"Zhao","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine and Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Pershad","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine and Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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