Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease
Year: 2025
Type: article
Study design: Observational Study
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=4.84×10 −8 ). SNP heritability for ANA+ was low (h 2 SNP = 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA− individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10 −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.
Source: Lupus Science & Medicine
Authors: 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
Institutions: Columbia University, Vanderbilt University Medical Center, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, The University of Texas Southwestern Medical Center, Children's Hospital of Philadelphia, Marshfield Clinic Research Foundation, Marshfield Clinic Research Institute, University of Alabama at Birmingham
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,391
Funders: Arthritis National Research Foundation, Children's Hospital of Philadelphia, Vanderbilt University, Northwestern University, Cincinnati Children's Hospital Medical Center, University of Washington, Lupus Research Alliance, Vanderbilt University Medical Center, Broad Institute, Georgia Clinical and Translational Science Alliance, King's College London, National Research Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1039948199, G1085576015, G1119622688, G1271251741, EHR-based Genomic Discovery and Implementation, G1531600799, G1569664509, G1678063915, G1764635170, G1766209448, G1800770867, G1875582626, G1967470738, G2103760183, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2310098089, G2328519459, G2424387874, G25420283, G2615776415, G2683268942, G2813733336, G2860569048, G2878691739, G2888548701, G2944859474, G303142226, G309706311, G3395468139, G3420921512, G3606196707, G3619590958, G364208108, G3791753988, G3938985443, G4049315607, G4203491109, Automated Storage and Retrieval of Biological Systems, G4324164867, G4395870004, G4410787187, G4857394517, G504300783, G556970706, G560889077, G5679716143, G5717004637, Genetic Epidemiology of Multiple Sclerosis, G6071621673, Genetic Discovery and Application in a Clinical Setting Continuing a Partnership, G635500700, G6589054092, G6764608945, G6975713648, G7163342664, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G8023087512, G8098630230, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, G8565821944, G858805679, G9000000364, G9000007771, G9000008449, G9000016172, G9000022508, G9000022789, G9000031451, G9000043901, G9000054231, G9000074171, G9000083571, G9000090229, G9000101053, G9000134904, G9000167145, G9000169515, G9000202130, G9000212326, G9000217501, G9000277114, G906879642, G911961363, G949362299, G95160140
OpenAlex ID: W4411295781