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We aimed to genetically identify PR by whole\u2010exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti\u2013citrullinated protein antibody (ACPA\u2212) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU\/liter). We conducted whole\u2010exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA\u2212 PR and ACPA+ PR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA\u2212. We identified 8 novel loci (in the ACPA\u2212 PR group: ZNF503, RPS6KL1, HOMER3, HLA\u2013DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA\u2212 PR group: HLA\u2013DRB1*0803 and HLA\u2013DQB1; in the ACPA+ PR group: HLA\u2013DPA1*0401) that were associated with PR and that surpassed genome\u2010wide significance (<jats:italic>P<\/jats:italic> &lt;\u20095 \u00d7\u200910<jats:sup>\u22128<\/jats:sup>). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R<jats:sup>2<\/jats:sup> &lt;\u20090.025), whereas ACPA+ PR and ACPA\u2212 PR showed a moderate genetic correlation (0.38 &lt; R<jats:sup>2<\/jats:sup> &lt;\u20090.8).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated the distinct genetic background between ACPA\u2212 and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42614","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T11:54:11Z","timestamp":1684842851000},"page":"1947-1957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using <scp>Whole\u2010Exome<\/scp> Sequencing"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4120-6676","authenticated-orcid":false,"given":"Chenxiang","family":"Zheng","sequence":"first","affiliation":[{"name":"Bio\u2010X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science Shanghai Jiao Tong University  Shanghai 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Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-296X","authenticated-orcid":false,"given":"Cui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Haematology and Rheumatology Shanghai Songjiang District Central Hospital  Shanghai PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology People's Hospital of Xinjiang Uygur Autonomous Region  Urumqi Xinjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing  Jiaxing Zhejiang 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