Background Although family history of arthritis-related diseases is routinely collected as part of the work-up for rheumatoid arthritis (RA) in clinical practice, the interpretation of such information is often difficult since the relative importance of a family history of different arthritic and inflammatory diseases - beyond the established familial association of RA itself - is little known. Further, recent studies suggest that seropositive and seronegative RA have unique as well as shared genetic risk factors. However, with the exception of the HLA region, little is known about which genes or pathways are different between the two disease subsets.
Objectives To assess the difference in predictive value of a family history of arthritis-related conditions for seropositive and seronegative RA, incidentally exploring the possible genetic difference of these disease subsets.
Methods Register-based nested case-control study in the Swedish total population. RA was ascertained through the nationwide Patient register and the Swedish Rheumatology Register. First degree relatives were ascertained through the Swedish Multi-Generation Register. Autoimmune and arthritis-related diseases in relatives were assessed through the Patient register. Familial risks where calculated using conditional logistic regression with robust standard errors.
Results Family history of seropositive RA was the strongest predictor of RA in the proband, regardless of serostatus. Statistically significant familial co-aggregation with RA was found for every arthritis-related disease under study, but risk increases varied widely (Table). With the exception of family history of RA itself, the difference in familial co-aggregation was very small for seropositive and seronegative RA. When combinations of family histories were examined, no arthritis-related disease added information beyond that provided by a family history of RA.
Conclusions Seropositive and seronegative RA does not appear to differ much in the genetic risk factors that are shared with other arthritis-related diseases. Although a family history of (either of) several non-RA arthritis-related diseases is predictive of RA, the impact of others (e.g., osteoarthritis, unspecified athralgia) is negligible.
Disclosure of Interest None declared