Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study

Abstract

Objective: The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability).

Methods: This study used the Taiwan National Health Insurance Research Database to identify all National Health Insurance registered beneficiaries (n = 23 658 577) in 2010; among them, 37 482 individuals had RA. We estimated familial RRs and 95% CIs of RA and other autoimmune diseases using marginal Cox proportional models and heritability of RA using a threshold liability model.

Results: The RR (95% CI) for RA was 328.27 (135.95, 795.63) for twins of RA patients; 11.97 (8.68, 16.52) for siblings; 4.86 (4.16, 5.67) for parents; 4.65 (3.92, 5.50) for offspring; and 2.32 (1.83, 2.95) for spouses. Using a threshold liability model, we estimated that familial transmission was 59.4% (95% CI: 50.3, 69.5%) and that heritability was 43.5% (33.9, 54.1%). The RR (95% CI) in individuals with a first-degree relative with RA was 2.91 (2.49, 3.42) for SLE; 2.92 (1.62, 5.25) for SSc; 3.13 (2.50, 3.93) for primary SS; 0.95 (0.36, 2.51) for idiopathic inflammatory myositis; 1.96 (1.54, 2.48) for type 1 diabetes mellitus; 3.32 (1.82, 5.95) for multiple sclerosis; 1.31 (1.31, 2.43) for IBD; 2.76 (2.46, 3.10) for AS; and 1.65 (1.54, 1.77) for psoriasis.

Conclusion: The risks of RA and other autoimmune diseases increased in individuals with an RA family history. Approximately two-thirds of RA phenotypic variation is explained by familial factors.

Keywords: familial aggregation; familial transmission; genetic epidemiology; heritability; rheumatoid arthritis.

Fig. 1

RA prevalence in people with a family history and the general population Individuals with a first-degree relative with RA (continuous line); general population (dashed line).