Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study.

• Published in: Annals of the Rheumatic Diseases
• Main Authors: Knevel, Rachel, Gröndal, Gerður, Huizinga, Tom W J, Visser, A Willemien, Jónsson, Helgi, Víkingsson, Arnór, Geirsson, Arni Jón, Steinsson, Kristján, van der Helm-van Mil, Annette H M
• Other Authors: Landspitali The National University Hospital, Reykjavík, Iceland. Leiden University Medical Center, The Netherlands.
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMJ Publishing Group 2012
• Subjects: Arthritis; Rheumatoid; Consanguinity; Databases; Factual; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Joints; Male; Middle Aged; Polymorphism; Single Nucleotide; Population Surveillance; Iceland
• Online Access: http://hdl.handle.net/2336/240172; https://doi.org/10.1136/annrheumdis-2011-200627

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. 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. 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. Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (p(KC)=0.018, p(IBD)=0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data. The severity of joint destruction in RA is influenced by genetic factors. Dutch Arthritis Foundation, Reumafonds Netherlands Organisation of Health Research and Development (ZonMw)