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<jats:title>Methods<\/jats:title>\n                    <jats:p>Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA\u2212) individuals without autoimmune disease and general controls who never had ANA testing performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA\u2212); an SNP upstream of the\n                      <jats:italic>TSBP1<\/jats:italic>\n                      in the HLA locus (rs1967688) was associated with ANA+ (p=4.84\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). SNP heritability for ANA+ was\u2009low (h\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>SNP<\/jats:sub>\n                      = 0.04), and the PRS for ANA+ was\u2009not significantly different in ANA+ and ANA\u2212 individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p&lt;2.2\u00d710\n                      <jats:sup>\u221216<\/jats:sup>\n                      ) but did not differ among ANA+, ANA\u2212 and general control groups (p=0.17).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      ANA+ occurring in the absence of autoimmune disease has a genetic association with the\n                      <jats:italic>HLA<\/jats:italic>\n                      region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2024-001476","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T23:55:22Z","timestamp":1749772522000},"page":"e001476","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease"],"prefix":"10.1136","volume":"12","author":[{"given":"Atlas","family":"Khan","sequence":"first","affiliation":[{"name":"Columbia University Vagelos College of Physicians and Surgeons, New York city, New York, 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