Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study.
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 (p(KC)=0.018, p(IBD)=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.
Department of Rheumatology, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands. r.knevel@lumc.nl
Rachel
R
Knevel
Gerður
G
Gröndal
Tom W J
TW
Huizinga
A Willemien
AW
Visser
Helgi
H
Jónsson
Arnór
A
Víkingsson
Arni Jón
AJ
Geirsson
Kristján
K
Steinsson
Annette H M
AH
van der Helm-van Mil
D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003241:Consanguinity; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007596:Joints / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance