Twin Concordance Rates for Rheumatoid Arthritis: Results From a Nationwide Study

Abstract

We report the concordance rate for RA in a nationwide study of 91 monozygotic (MZ) and 112 dizygotic (DZ) pairs. Twin pairs were recruited from both a national media campaign and a 2-month prospective inquiry of all UK rheumatologists. Disease status was established following a structured clinical and serological appraisal, together with radiological assessment where necessary. Zygosity was confirmed using DNA fingerprinting. In all, 14 (15.4%) of the MZ and four (3.6%) of the DZ pairs were disease concordant (risk ratio: 4.3 95% CI 1.5 to 12.6). There was no difference in the concordance between the media and clinical derived twins. Further the excess MZ concordance persisted after adjusting for age, age at disease onset, sex and rheumatoid factor status. Analysing the data in relation to the timing of disease onset in the first affected twin showed that subsequent disease risk in the initially unaffected co-twins of the MZ affected probands increased with increasing duration of follow-up. We conclude that the overall MZ concordance at 15% is lower than the 30% figure normally quoted from a study some 30 years ago and sets a ceiling at the potential genetic contribution to disease susceptibility.

STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians

“…1 Although RA and SLE are considered as idiopathic diseases, both the higher concordance rates and familial aggregation indicate a significant genetic influence on their pathogenesis. [2][3][4] Human leukocyte antigen genes are the strongest genetic locus known to be associated with susceptibility to both diseases. 5,6 Nevertheless, genome-wide linkage studies have shown several non-human leukocyte antigen loci influencing their susceptibility risk.…”

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

“…1 Twin concordance rate analyses and recently genome scan analyses give important insights into the genetic background of RA. [2][3][4][5][6] The QK(R)RAA shared epitope that is present in HLA DRB1*0401, DRB1*0101, and DRB*0404 genotypes is associated with the occurrence of RA, extraarticular manifestations, and a more severe course of RA. 7 This observation is suggestive of an important role for adaptive immune processes, and in particular for the interaction of antigen presenting and T cells in RA pathogenesis.…”

Dense genome‐wide linkage analysis of rheumatoid arthritis, including covariates

“…mean concordance rate of 12% in monozygotic twins, 4 times higher than in dizygotic twins (3)(4)(5)(6). Our group (the European Consortium on Rheumatoid Arthritis Families [see Appendix A]), a Japanese group, the North American Rheumatoid Arthritis Consortium, and a British group have performed genome scans with different marker sets and an average marker spacing ranging from 10 cM to 12 cM (7)(8)(9)(10)(11).…”