{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:53:35Z","timestamp":1781304815750,"version":"3.54.1"},"reference-count":25,"publisher":"The Journal of Rheumatology","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We examined the association between schizophrenia genetic susceptibility loci and neuropsychiatric systemic lupus erythematosus (NPSLE) features in childhood-onset SLE (cSLE) participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Study participants from the Lupus Clinic at the Hospital for Sick Children, Toronto, met \u2265 4 of the American College of Rheumatology and\/or SLE International Collaborating Clinics SLE classification criteria and were genotyped using the Illumina Multi-Ethnic Global Array or the Global Screening Array. Ungenotyped single-nucleotide polymorphisms (SNPs) were imputed, and ancestry was genetically inferred. We calculated 2 additive schizophrenia-weighted polygenic risk scores (PRS) using (1) genome-wide significant SNPs (<jats:italic>P<\/jats:italic> &lt; 5 \u00d7 10<jats:sup>\u20138<\/jats:sup>), and (2) an expanded list of SNPs with significance at <jats:italic>P<\/jats:italic> &lt; 0.05. We defined 2 outcomes compared to absence of NPSLE features: (1) any NPSLE feature, and (2) subtypes of NPSLE features (psychosis and nonpsychosis NPSLE). We completed logistic and multinomial regressions, first adjusted for inferred ancestry only and then added for variables significantly associated with NPSLE in our cohort (<jats:italic>P<\/jats:italic> &lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 513 participants with cSLE. Median age at diagnosis was 13.8 years (IQR 11.2\u201315.6), 83% were female, and 31% were of European ancestry. An increasing schizophrenia genome-wide association PRS was not associated with NPSLE (OR 1.04, 95% CI 0.87\u20131.26, <jats:italic>P<\/jats:italic> = 0.62), nor with the NPSLE subtypes, psychosis (OR 0.97, 95% CI 0.73\u20131.29, <jats:italic>P<\/jats:italic> = 0.84) and other nonpsychosis NPSLE (OR 1.08, 95% CI 0.88\u20131.34, <jats:italic>P<\/jats:italic> = 0.45), in ancestry-adjusted models. Results were similar for the model including covariates (ancestry, malar rash, oral\/nasal ulcers, arthritis, lymphopenia, Coombs-positive hemolytic anemia, lupus anticoagulant, and anticardiolipin antibodies) and for the expanded PRS estimates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We did not observe an association between known risk loci for schizophrenia and NPSLE in a multiethnic cSLE cohort. This work warrants further validation.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.210363","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T12:25:26Z","timestamp":1633091126000},"page":"192-196","source":"Crossref","is-referenced-by-count":6,"title":["Schizophrenia Genetics and Neuropsychiatric Features in Childhood-onset Systemic Lupus Erythematosus"],"prefix":"10.3899","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-8539","authenticated-orcid":false,"given":"Ana C.","family":"Ulloa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangming","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella L.","family":"Carlomagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-2494","authenticated-orcid":false,"given":"Daniela","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1023-9499","authenticated-orcid":false,"given":"Deborah M.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-8148","authenticated-orcid":false,"given":"Linda T.","family":"Hiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"2022062401251320000_49.2.192.1","doi-asserted-by":"crossref","first-page":"16021","DOI":"10.1038\/ncomms16021","article-title":"Transancestral mapping and genetic load in systemic lupus erythematosus","volume":"8","author":"Langefeld","year":"2017","journal-title":"Nat Commun"},{"key":"2022062401251320000_49.2.192.2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.150884"},{"key":"2022062401251320000_49.2.192.3","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F"},{"key":"2022062401251320000_49.2.192.4","first-page":"1536","article-title":"The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus","volume":"29","author":"Sibbitt","year":"2002","journal-title":"J Rheumatol"},{"key":"2022062401251320000_49.2.192.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.09.019"},{"key":"2022062401251320000_49.2.192.6","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/art.40697","article-title":"Long-term clinical outcomes in a cohort of adults with childhood-onset systemic lupus erythematosus","volume":"71","author":"Groot","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2022062401251320000_49.2.192.7","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.121096"},{"key":"2022062401251320000_49.2.192.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature13595"},{"key":"2022062401251320000_49.2.192.9","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1001\/jamapsychiatry.2019.2850","article-title":"Genome-wide association of endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) study","volume":"76","author":"Greenwood","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"2022062401251320000_49.2.192.10","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1093\/hmg\/ddz145","article-title":"Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk","volume":"28","author":"Pouget","year":"2019","journal-title":"Hum Mol Genet"},{"key":"2022062401251320000_49.2.192.11","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32652"},{"key":"2022062401251320000_49.2.192.12","doi-asserted-by":"publisher","DOI":"10.1002\/art.34473"},{"key":"2022062401251320000_49.2.192.13","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"2022062401251320000_49.2.192.14","unstructured":"Infinium Expanded Multi-Ethnic Genotyping Array . 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