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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引用次数: 0
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 (h2SNP= 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.
期刊介绍：
Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.
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