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Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study
  1. Rachel Knevel1,
  2. Gerður Gröndal2,
  3. Tom W J Huizinga1,
  4. A Willemien Visser1,
  5. Helgi Jónsson2,
  6. Arnór Víkingsson2,
  7. Árni Jón Geirsson2,
  8. Kristján Steinsson2,
  9. Annette H M van der Helm-van Mil1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Landspítali, National University Hospital Center for Rheumatology Research, Reykjavik, Iceland
  1. Correspondence to Rachel Knevel, Department of Rheumatology, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands; r.knevel{at}lumc.nl

Abstract

Background The susceptibility to rheumatoid arthritis (RA) is partly heritable, but whether the severity of RA is also influenced by genetics has not been determined. The evaluation of the heritability of the severity of RA is basic to further studies on genetic factors. A study was undertaken to determine whether joint destruction is heritable.

Methods Iceland has an unique comprehensive genealogy database covering today's population and stretching back to ≥1000 years ago, as well as genome-wide single nucleotide polymorphism data for a large part of the population. Hand and feet x-rays of 325 Icelandic patients with RA were scored according to the Sharp-van der Heijde method. The degree of relatedness between patients was estimated in two ways: (1) kinship coefficients (KC) on the genealogical data were expressed; and (2) the identical-by-descent (IBD) was estimated applying long-range phasing of the genetic profile of the patients. The degree of relatedness was tested against the similarity in joint destruction rates by linear regression analysis and the heritability of joint destruction was calculated.

Results Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (pKC=0.018, pIBD=0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data.

Conclusions The severity of joint destruction in RA is influenced by genetic factors.

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Footnotes

  • Funding The work of RK was supported by the Dutch Arthritis Foundation, Reumafonds. AHMvdHvM was supported by Netherlands Organisation of Health Research and Development (ZonMw).

  • Ethical approval Permission was obtained from the National Ethical Committee and all patients gave their informed consent.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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