{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:45:06Z","timestamp":1790520306649,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T00:00:00Z","timestamp":1466726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"crossref","award":["20385"],"award-info":[{"award-number":["20385"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIHR Manchester Musculoskeletal Biomedical Research Unit"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic polymorphisms within the HLA region explain only a modest proportion of anti\u2013cyclic citrullinated peptide (anti\u2010CCP)\u2013negative rheumatoid arthritis (RA) heritability. However, few non\u2010HLA markers have been identified so far. This study was undertaken to replicate the associations of anti\u2010CCP\u2013negative RA with non\u2010HLA genetic polymorphisms demonstrated in a previous study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:bold>The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune\u2010related regions in<\/jats:bold> <jats:bold>3,339 anti\u2010CCP\u2013negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case\u2013control replication study of the anti\u2010CCP\u2013negative markers with the strongest associations in that discovery study, in an independent cohort of anti\u2010CCP\u2013negative UK RA patients. Individuals from the arcOGEN<\/jats:bold> <jats:bold>Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome\u2010wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:bold>After genotyping and imputation quality control procedures, data were available for 15 non\u2010HLA single\u2010nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers <jats:italic>ANKRD55<\/jats:italic> (meta\u2010analysis odds ratio [OR] 0.80; <jats:italic>P<\/jats:italic>\u2009=\u20092.8 \u00d7 10<jats:sup>\u221213<\/jats:sup>)<\/jats:bold> <jats:bold>and <jats:italic>BLK<\/jats:italic> (OR 1.13; <jats:italic>P<\/jats:italic>\u2009=\u20097.0 \u00d7 10<jats:sup>\u22126<\/jats:sup>) and identified new and specific markers of anti\u2010CCP\u2013negative RA (prolactin [<jats:italic>PRL<\/jats:italic>] [OR 1.13; <jats:italic>P<\/jats:italic>\u2009=\u20092.1 \u00d7 10<jats:sup>\u22126<\/jats:sup>] and <jats:italic>NFIA<\/jats:italic> [OR 0.85; <jats:italic>P<\/jats:italic>\u2009=\u20092.5 \u00d7 10<jats:sup>\u22126<\/jats:sup>]). Neither of these loci is associated with other common, complex autoimmune diseases.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:bold>Anti\u2010CCP\u2013negative RA and anti\u2010CCP\u2013positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the <jats:italic>PRL<\/jats:italic> and <jats:italic>NFIA<\/jats:italic> genes represent examples of genetic susceptibility factors specific for anti\u2010CCP\u2013negative RA.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39619","type":"journal-article","created":{"date-parts":[[2016,2,20]],"date-time":"2016-02-20T10:48:21Z","timestamp":1455965301000},"page":"1603-1613","source":"Crossref","is-referenced-by-count":44,"title":["Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti\u2013Cyclic Citrullinated Peptide\u2013Negative Rheumatoid Arthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Sebastien","family":"Viatte","sequence":"first","affiliation":[{"name":"Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Science Centre, and University of Manchester Manchester 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