Family History of Rheumatic, Autoimmune, and Nonautoimmune Diseases and Risk of Rheumatoid Arthritis

Objective: Since comorbidities such as autoimmune diseases may be associated with rheumatoid arthritis (RA) risk, we hypothesized that a family history of these other conditions might also predict RA. Therefore, we aimed to determine the association between family history of 79 comorbidities and RA. Methods: This case–control study identified 821 cases of RA in the Mayo Clinic Biobank (positive predictive value 95%) and matched 3 controls to each case based on age, sex, recruitment year, and location. Patients self reported family history and characteristics (adjusted). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for RA risk according to the presence of family history for each comorbidity, adjusted for body mass index, race, and smoking. Results: Family history of several conditions was associated with developing RA, including rheumatic autoimmune diseases (OR_adj 1.89 [95% CI 1.41–2.52]), pulmonary fibrosis (OR_adj 2.12 [95% CI 1.16–3.80]), inflammatory bowel disease (OR_adj 1.45 [95% CI 1.05–1.98]), hyper/hypothyroidism (OR_adj 1.34 [95% CI 1.10–1.63]), and obstructive sleep apnea (OR_adj 1.28 [95% CI 1.05–1.55]). Parkinson’s disease and type 2 diabetes mellitus were associated with a statistically decreased risk of RA that did not reach the prespecified significance threshold of P < 0.01 (OR_adj 0.70 [95% CI 0.49–0.98] and OR_adj 0.81 [95% CI 0.67–0.97], respectively). Analyses among 143 cases of incident RA were similar and also suggested an association with a family history of autism (OR 10.5 [95% CI 2.51–71.3]). Conclusion: Family history of several autoimmune and nonautoimmune comorbidities was associated with increased risk of RA, providing an opportunity to identify novel populations at risk for RA.