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Abstract
BackgroundRheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population.Methods and FindingsIn a mail survey addressed to 56.707 twin individuals, RA was reported by 479 individuals, mean age 52 (range 16–73). Respondents underwent an interview and clinical examination. Ascertainment probability was 80%. RA was confirmed in 162 twin individuals yielding a prevalence at 0.37% (95% CI 0.31–0.43). The mean discordance time was 19 years (range 0–57). The concordance was 9.1% (95% CI 1.9 to 24.3) in MZ, 6.4% (95% CI 2.1 to 14.3) in DZss. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins. The correlation coefficients were 0.60 (0.33 to 0.78) in monozygotic (MZ) and 0.55 (0.33 to 0.72) in dizygotic same sexed (DZss) pairs. Twelve percent (95% CI 0–76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0–72%) to shared environmental effects and 38% (95% CI 17–61%) to non-shared environmental effects.ConclusionsThis study emphasizes that family factors are important for the development of RA. Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant. However, it should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets.
Highlights
This study emphasizes that family factors are important for the development of Rheumatoid arthritis (RA)
It should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets
[1] Its origin remains elusive but there is evidence, that both genetic and environmental triggers are implicated in the pathogenesis and growing evidence suggests that RA consists of at least 2 different subsets characterized by the presence or absence of antibodies to citrullinated protein antigen (ACPA)
Summary
Rheumatoid arthritis (RA) is a chronic systemic disorder with autoimmune traits in which polyarticular synovitis is prominent. [1] Its origin remains elusive but there is evidence, that both genetic and environmental triggers are implicated in the pathogenesis and growing evidence suggests that RA consists of at least 2 different subsets characterized by the presence or absence of antibodies to citrullinated protein antigen (ACPA). [2] Newly published genome-wide association studies (GWAS) have demonstrated several DNA sequence variations associated with RA. [3] In a recent GWA metaanalysis it was estimated that current genetic discoveries account for around 16% of the disease variance, [4] more than half of the liability to RA was considered to be genetic, [5] regardless of autoantibody status. [6]The most cited heritability estimate at around 60% is derived from 2 previous twin studies. [8] The probandwise and the pairwise concordance estimate in the Finnish study was 22.0% and 12.3% in monozygotic (MZ) twins and 6.7% and 3.5% in dizygotic same sexed (DZss) twins. The pairwise concordance estimate was 15.4% in MZ twins and 3.6% in sameand opposite sexed dizygotic (DZss/os) twins in the UK study. [10] Our purpose was, based on this large and ethnically homogenous population of RA twins, to provide an optimized heritability estimate on RA and to study the recurrence risk of the disease. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population
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