{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T18:34:47Z","timestamp":1781548487267,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using analyses of variance, chi\u2010square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA\u2010SE) with all participant groups, both unstratified and stratified for anti\u2013citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients). CSA patients were assessed for conversion to inflammatory arthritis over a period of 2\u2009years, after which they were classified as either CSA converters (n\u00a0=\u00a084) or CSA nonconverters (n\u00a0=\u00a0395).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PRS was increased in RA patients (mean \u00b1 SD PRS 1.31 \u00b1\u20090.96) compared to the complete CSA group (1.07 \u00b1\u20090.94) and compared to CSA converters (1.12 \u00b1\u20090.94). In ACPA\u2013 strata, PRS distributions differed strongly when comparing the complete CSA group (mean \u00b1 SD PRS 1.05 \u00b1\u20090.94) and CSA converters (0.97 \u00b1\u20090.87) to RA patients (1.20 \u00b1\u20090.94), while in the ACPA+ strata, the complete CSA group (1.25 \u00b1\u20090.99) differed clearly from healthy controls (1.05 \u00b1\u20090.94) and RA patients (1.41 \u00b1\u20090.96). HLA\u2010SE was more prevalent in the RA group (prevalence 0.64) than the complete CSA group (0.45), with small differences between RA patients and CSA converters (0.64 versus 0.60) and larger differences between CSA converters and CSA nonconverters (0.60 versus 0.42). HLA\u2010SE prevalence differed more strongly within the ACPA+ strata as follows: healthy controls (prevalence 0.43), CSA nonconverters (0.48), complete CSA group (0.59), CSA converters (0.66), and RA patients (0.79).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We observed that genetic predisposition increased across pre\u2010RA participant groups. The RA PRS differed in early classified RA and inflammatory pre\u2010disease stages, regardless of ACPA stratification. HLA\u2010SE prevalence differed between arthritis patients, particularly ACPA+ patients, and healthy controls. Genetics seem to fulfill different etiologic roles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42323","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T03:13:05Z","timestamp":1660273985000},"page":"178-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Genetics in Clinically Suspect Arthralgia and Rheumatoid Arthritis Development: A Large Cross\u2010Sectional Study"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-6232","authenticated-orcid":false,"given":"Marc P.","family":"Maurits","sequence":"first","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-4043","authenticated-orcid":false,"given":"Fenne","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-3817","authenticated-orcid":false,"given":"Ellis","family":"Niemantsverdriet","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W. J.","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik B.","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences Leiden Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Le Cessie","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette H. M.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-3023","authenticated-orcid":false,"given":"Rachel","family":"Knevel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Leiden University Medical Center, The Netherlands, and Translational &amp; Clinical Research Institute, Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205522"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209846"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2017-000479"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213678"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27366"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.013"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0353-1"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq230"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040278"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3643"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay1548"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064683"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21385"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208138"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21739"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42323","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.42323","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:56:49Z","timestamp":1759931809000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/art.42323"],"URL":"https:\/\/doi.org\/10.1002\/art.42323","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"assertion":[{"value":"2022-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}