Clustering of disease features within 512 multicase rheumatoid arthritis families

Objective. To determine whether specific rheumatoid arthritis (RA) disease features demonstrate the presence of significant familial clustering. Methods. We studied 1,097 individuals with RA from 512 multicase families enrolled in the North American Rheumatoid Arthritis Consortium. All patients were interviewed and examined to collect standardized information about demographic and clinical characteristics. Affected individuals also underwent radiography of the hands and wrists and were genotyped for the HLA-DRB1 shared epitope. Familial clustering of disease features was assessed using contingency table analysis and Pearson correlation coefficients. Multivariate logistic and linear regression analyses were used to account for other characteristics that might influence familial clustering, such as disease duration, sex, and age at diagnosis. Results. Several disease characteristics exhibited significant familial clustering, including seropositivity (multivariate odds ratio [OR] 4.3, P < 0.0001), nodules (OR 2.3, P < 0.0001), and age at RA diagnosis (multivariate regression coefficient [beta] 0.44, P < 0.0001). Other characteristics demonstrated statistically significant but modest degrees of familial clustering (joint Alignment and Motion score, Health Assessment Questionnaire score, and year of RA diagnosis) or modest but nonsignificant familial clustering (other extraarticular manifestations, other autoimmune diseases). Conclusion. The clustering of certain disease characteristics implicates specific genetic or nongenetic causes. These results highlight the importance of considering disease phenotype in future genetic and epidemiologic studies of RA.