Genetics of Antinuclear Antibodies

Antinuclear antibodies (ANA) are antibodies that react against self-antigens in the cell. While it has been reported that 12 to 20% of the general population have a positive ANA test, the genetics of ANA positivity is unknown. We performed a genome wide-association study for positive ANA tests among individuals without an ANA related autoimmune disease in the Vanderbilt University Medical Center (VUMC) DNA biobank linked to the de-identified electronic health record (EHR) system. The study is funded by the National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) grant R01AR076516.]]>
In a clinical biobank (BioVU), we studied 5079 individuals without an autoimmune disease who had an antinuclear antibody (ANA) test performed as part of their clinical care and went through genome-wide interrogation in the Illumina Infinium Multi-Ethnic Genotyping Array (MEGA) platform, Cases were defined as individuals with ANA titer of 1:80 or higher and controls had only negative ANA results. Principal components (PCs) for ancestry were calculated using common variants (MAF>1%) with high variant call rate (>98%), excluding SNPs that deviated from Hardy-Weinberg equilibrium (HWE, p<1x10-6), and SNPs in linkage. The associations are restricted to individuals of European ancestry defined by principal components (±4 SD of the median values for Whites of European ancestry from the HapMap reference). Covariates in the additive model include principal components, year of birth, and sex.Inclusion criteria: Individuals of European ancestry who had ANA tests performed as part their clinical care and had been genotyped in Illumina Infinium Multi-Ethnic Genotyping Array (MEGAEX) platform as part of VUMC initiative were included. Cases were defined as any individual with an ANA test with a titer of 1:80 or higher and controls only had negative ANA test in the EHR. Exclusion criteria: Individuals with a billing code for an ANA-related autoimmune disease including: systemic lupus erythematosus; cutaneous lupus; Sjögren's syndrome; scleroderma; diffuse diseases of connective tissue; dermatomyositis; polymyositis; undifferentiated connective tissue disease; rheumatoid arthritis-related phenotypes; juvenile rheumatoid arthritis; Crohn's disease; ulcerative colitis; autoimmune thyroiditis-related phenotypes; autoimmune hepatitis; autoimmune hemolytic anemias; primary biliary cirrhosis; and other autoimmune related disorders were excluded from the analyses.Individuals with a positive ANA test with a titer of 1:40 or missing titer information were also excluded.]]>