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

作者：Liao Katherine P^*; Kurreeman Fina; Li Gang; Duclos Grant; Murphy Shawn; Guzman Raul; Cai Tianxi; Gupta Namrata; Gainer Vivian; Schur Peter; Cui Jing; Denny Joshua C; Szolovits Peter; Churchill Susanne; Kohane Isaac; Karlson Elizabeth W; Plenge Robert M

来源：Arthritis and Rheumatism, 2013, 65(3): 571-581.

DOI：10.1002/art.37801

Objective The significance of nonrheumatoid 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 anticitrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), antitissue transglutaminase antibodies (AGTAs), and antithyroid 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 %26lt; 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 105) and non-RA controls (P = 5.0 x 103). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjogren%26apos;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.

• 出版日期2013-3
• 单位MIT