Dr. Schur receives royalties from UptoDate in Rheumatology.
Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non–rheumatoid arthritis controls
Article first published online: 25 FEB 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 3, pages 571–581, March 2013
How to Cite
Liao, K. P., Kurreeman, F., Li, G., Duclos, G., Murphy, S., Guzman, R., Cai, T., Gupta, N., Gainer, V., Schur, P., Cui, J., Denny, J. C., Szolovits, P., Churchill, S., Kohane, I., Karlson, E. W. and Plenge, R. M. (2013), Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non–rheumatoid arthritis controls. Arthritis & Rheumatism, 65: 571–581. doi: 10.1002/art.37801
- Issue published online: 25 FEB 2013
- Article first published online: 25 FEB 2013
- Accepted manuscript online: 10 DEC 2012 09:34AM EST
- Manuscript Accepted: 15 NOV 2012
- Manuscript Received: 6 SEP 2012
- NIH. Grant Numbers: U54-LM-008748, K08-AR-060257, K24-AR-052403, R01-AR-049880, P60-AR-047782, R01-AR-057108, R01-AR-056768, U01-GM-092691, R01-AR-059648
- Katherine Swan Ginsburg Fund
- Career Award for Medical Scientists from the Burroughs Wellcome Fund
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.
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.
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 × 10−5) and non-RA controls (P = 5.0 × 10−3). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjögren's/sicca syndrome in RA cases.
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.