Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls

Citation:

Liao KP, Kurreeman F, Li G, Duclos G, Murphy S, Guzman R, Cai T, Gupta N, Gainer V, Schur P, et al. Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls. Arthritis and rheumatismArthritis and rheumatismArthritis and rheumatism. 2013;65 :571-81.

Date Published:

Mar

Abstract:

OBJECTIVE: The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls. METHODS: Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers. The levels of anti-citrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), anti-tissue transglutaminase antibodies (AGTAs), and anti-thyroid peroxidase (anti-TPO) antibodies were measured. All subjects were genotyped for autoimmune risk alleles, and the association between number of autoimmune risk alleles present and number of types of autoantibodies present was studied. A phenome-wide association study (PheWAS) was conducted to study potential associations between autoantibodies and clinical diagnoses among RA cases and non-RA controls. RESULTS: The mean ages were 60.7 years in RA cases and 64.6 years in non-RA controls. The proportion of female subjects was 79% in each group. The prevalence of ACPAs and ANAs was higher in RA cases compared to controls (each P < 0.0001); there were no differences in the prevalence of anti-TPO antibodies and AGTAs. Carriage of higher numbers of autoimmune risk alleles was associated with increasing numbers of autoantibody types in RA cases (P = 2.1 x 10(-5)) and non-RA controls (P = 5.0 x 10(-3)). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjogren's/sicca syndrome in RA cases. CONCLUSION: The increased frequency of autoantibodies in RA cases and non-RA controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS of EMR data, with linkage to laboratory data obtained from blood samples, provide a novel method to test for the clinical significance of biomarkers in disease.

Notes:

Liao, Katherine PKurreeman, FinaLi, GangDuclos, GrantMurphy, ShawnGuzman, RaulCai, TianxiGupta, NamrataGainer, VivianSchur, PeterCui, JingDenny, Joshua CSzolovits, PeterChurchill, SusanneKohane, IsaacKarlson, Elizabeth WPlenge, Robert MK08 AR060257/AR/NIAMS NIH HHS/K08-AR-060257/AR/NIAMS NIH HHS/K24 AR052403/AR/NIAMS NIH HHS/K24-AR-052403/AR/NIAMS NIH HHS/P60 AR047782/AR/NIAMS NIH HHS/P60-AR-047782/AR/NIAMS NIH HHS/R01 AR049880/AR/NIAMS NIH HHS/R01 AR056768/AR/NIAMS NIH HHS/R01 AR059648/AR/NIAMS NIH HHS/R01-AR-049880/AR/NIAMS NIH HHS/R01-AR-056768/AR/NIAMS NIH HHS/R01-AR-057108/AR/NIAMS NIH HHS/R01-AR-059648/AR/NIAMS NIH HHS/U01 GM092691/GM/NIGMS NIH HHS/U01-GM-092691/GM/NIGMS NIH HHS/U54 LM008748/LM/NLM NIH HHS/U54-LM-008748/LM/NLM NIH HHS/Arthritis Rheum. 2013 Mar;65(3):571-81. doi: 10.1002/art.37801.