{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:26:05Z","timestamp":1785270365794,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,28]],"date-time":"2017-01-28T00:00:00Z","timestamp":1485561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32\u2010AR\u2010059039"],"award-info":[{"award-number":["T32\u2010AR\u2010059039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)\u2013based phenome\u2010wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A validated algorithm identified RA subjects from the de\u2010identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti\u2013cyclic citrullinated peptide antibody (ACPA) values. We tested EHR\u2010derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in RF\u2010positive versus RF\u2010negative subjects and ACPA\u2010positive versus ACPA\u2010negative subjects. Following PheWAS, select phenotypes were then manually reviewed, and fibromyalgia was specifically evaluated using a validated algorithm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, <jats:italic>P<\/jats:italic>\u2009=\u20093.7 \u00d7 10<jats:sup>\u221210<\/jats:sup>) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, \u223c80% had fibromyalgia. Follow\u2010up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR 1.8, <jats:italic>P<\/jats:italic>\u2009=\u20094.0 \u00d7 10<jats:sup>\u22126<\/jats:sup>). Seropositive RA was associated with chronic airway obstruction (OR 2.2, <jats:italic>P<\/jats:italic>\u2009=\u20091.4 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and tobacco use (OR 2.2, <jats:italic>P<\/jats:italic>\u2009=\u20097.0 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39851","type":"journal-article","created":{"date-parts":[[2016,9,2]],"date-time":"2016-09-02T14:02:37Z","timestamp":1472824957000},"page":"291-300","source":"Crossref","is-referenced-by-count":38,"title":["Phenome\u2010Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia"],"prefix":"10.1002","volume":"69","author":[{"given":"Jayanth","family":"Doss","sequence":"first","affiliation":[{"name":"Duke University Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Mo","sequence":"additional","affiliation":[{"name":"Loma Linda University Medical Center Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Vanderbilt University Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J.","family":"Crofford","sequence":"additional","affiliation":[{"name":"Vanderbilt University Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Denny","sequence":"additional","affiliation":[{"name":"Vanderbilt University Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_6_3_1","unstructured":"BRASS: Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study web site. 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