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THU0105 Familial Risks of RA in Relation to Type of Affected Relatives, Age, Sex, and RF/ACPA
  1. T. Frisell1,
  2. M. Holmqvist1,
  3. H. Källberg2,
  4. L. Klareskog1,
  5. L. Alfredsson2,
  6. L. Padyukov1,
  7. J. Askling1
  1. 1Department of Medicine
  2. 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Background Although it is widely accepted that RA aggregates in families, population-based studies are few. The magnitude of the aggregation and whether it differs by disease characteristics also remains unclear.

Objectives To estimate the familial aggregation of RA in three population-representative samples, and to test if familial aggregation is modified by type of relative, sex, RF/ACPA status, and age at RA onset.

Methods Register-based case-control study in the Swedish total population. RA was ascertained through the nationwide Patient register (N=88639), the clinical Swedish Rheumatology Quality register (N=11519), and the EIRA case-control study (N=2871). First and second degree relatives were ascertained through the Swedish Multi-Generation Register. Familial risks and 95% confidence intervals (CI) where calculated using conditional logistic regression and expressed as odds ratios (OR).

Results Consistent across data sources, the familial OR for RA was about 3 in first degree relatives of RA patients, and 2 in second degree relatives. The familial risks were similar among siblings (OR=3.6 (3.1-4.0)), parents (3.1 (2.9 -3.3)) and offspring (3.2 (3.0 - 3.5)). Familial aggregation was not modified by sex, but was higher for RA with early onset and for seropositive RA. The familial aggregation was most pronounced for ACPA+ disease, while the familiality of seronegative disease was similar as the cross-phenotype risks (Table). The observed familial risks were consistent with a heritability for ACPA+ RA of around 50% and for ACPA- RA of about 20%.

Conclusions The pattern of risks suggests that familial factors influence RA in men and women equally, and that these factors are more important for early onset RA. Familial factors are more important for seropositive RA, but there is a significant familial overlap between seropositive and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest a heritability of RA lower than previously reported, in particular for ACPA- RA.

Disclosure of Interest None Declared

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