{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:58:25Z","timestamp":1792803505960,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01\u2010AI\u2010097134"],"award-info":[{"award-number":["R01\u2010AI\u2010097134"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"\n Objective<\/jats:title>\n Antinuclear antibodies (ANA) are detected in up to 14% of the population, and many individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity is limited. In this study, we aimed to perform a genome\u2010wide association study of asymptomatic ANA positivity in multiple populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Asymptomatic individuals who were either ANA positive or ANA negative from the All of Us Research Program were included in this study, selecting those with an ANA test performed by immunofluorescence and no evidence of autoimmune disease. Imputation was performed, and a multipopulation meta\u2010analysis including approximately 6 million single\u2010nucleotide polymorphisms (SNPs) was conducted. Genome\u2010wide SNP\u2010based heritability was estimated using the Genome\u2010wide Complex Trait Analysis\u00a0software. A cumulative genetic risk score for lupus was constructed using previously reported genome\u2010wide significant loci.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals across three populations were included. The multipopulation meta\u2010analysis revealed SNPs with a suggestive association (\n P<\/jats:italic>\n <1 \u00d7 10\n \u22125<\/jats:sup>\n ) across 8 different loci, but no genome\u2010wide significant loci were identified. A gene variant upstream of\n HLA\u2010DQB1<\/jats:italic>\n , (rs17211748,\n P<\/jats:italic>\n = 1.4 \u00d7 10\n \u22126<\/jats:sup>\n , odds ratio 0.82, 95% confidence interval 0.76\u20130.89), showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Individuals who were asymptomatic and ANA positive did not exhibit increased cumulative genetic risk for lupus compared with individuals who were ANA negative.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n ANA production is not associated with significant genetic risk and is primarily determined by environmental factors.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.43032","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T01:49:42Z","timestamp":1729216182000},"page":"356-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Analysis of Asymptomatic Antinuclear Antibody Production"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-8740","authenticated-orcid":false,"given":"Mehmet","family":"Hocao\u01e7lu","sequence":"first","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4928-3545","authenticated-orcid":false,"given":"Desir\u00e9","family":"Casares\u2010Marfil","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-962X","authenticated-orcid":false,"given":"Amr H.","family":"Sawalha","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh 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