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PubMed · 40514052

Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.

Atlas Khan·Gul Karakoc·Ge Liu·Jacy Zanussi·Nancy J Olsen·Mingjian Shi·Nancy J Cox·Jonathan Mosley·Charles Michael Stein·Krysztof Kiryluk·Wei-Qi Wei·Frank Mentch·Scott Hebbring·James Linneman·Vivian Kawai
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Abstract

OBJECTIVE: We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE. METHODS: 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-) individuals without autoimmune disease and general controls who never had ANA testing performed. RESULTS: A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the TSBP1 in the HLA locus (rs1967688) was associated with ANA+ (p=4.84&#xd7;10-8). SNP heritability for ANA+ was&#x2009;low (h2 SNP= 0.04), and the PRS for ANA+ was&#x2009;not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2&#xd7;10-16) but did not differ among ANA+, ANA- and general control groups (p=0.17). CONCLUSIONS: ANA+ occurring in the absence of autoimmune disease has a genetic association with the HLA 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.

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HumansLupus Erythematosus, SystemicGenome-Wide Association StudyPolymorphism, Single NucleotideCase-Control StudiesAntibodies, AntinuclearFemaleMaleGenetic Predisposition to DiseaseAdultMiddle AgedWhite PeopleAutoimmune DiseasesMultifactorial Inheritanceautoantibodieslupus erythematosus, systemicpolymorphism, geneticrisk factorsJournal ArticleResearch Support, N.I.H., Extramural

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Atlas Khan, Gul Karakoc, Ge Liu, Jacy Zanussi, Nancy J Olsen, Mingjian Shi, Nancy J Cox, Jonathan Mosley, Charles Michael Stein, Krysztof Kiryluk, Wei-Qi Wei, Frank Mentch, Scott Hebbring, James Linneman, Vivian Kawai. 2025-06-12. Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.. https://doi.org/10.1136/lupus-2024-001476

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