The inheritance of rheumatoid arthritis in Iceland

Objective. Rheumatoid arthritis (RA) is the most common form of inflammator y arthritis. Although there is a large body of evidence suggesting that RA is immune mediated, the etiology remains unresolved. Twin studies have show n disease concordance rates of similar to 15% in monozygotic twins and 4% i n dizygotic twins, while the estimated risk ratio for siblings of RA patien ts ranges from 5 to 8. Our goal was to use genealogic data from Iceland to further investigate the genetic component of RA. Methods. Data were obtained from a population-based, computerized genealogy database that was developed to examine multigenerational relationships amo ng individuals in the relatively homogeneous population of Iceland. Using a n algorithm, the minimum founder test, we calculated the least number of fo unders required to account for a list of RA patients, and compared it with 1,000 sets of same-sized matched control groups. In addition, we estimated the kinship coefficient and risk ratios for relatives of the RA patients. Results. Several familial clustering tests demonstrated that the RA patient s were more related to each other than were the average control set of Icel anders. A significantly fewer number of founders was necessary to account f or our patient list than for the random sets of matched controls (P < 0.001 ), and the average pairwise identity-by-descent sharing was greater among t he patients than among the control sets (P < 0.001). In addition, there was an increased risk of RA in first- and second-degree relatives of the patie nts; e.g., for siblings, the risk ratio was 4.38 (95% confidence interval 3 .26-5.67), and for uncles/aunts, the risk ratio was 1.95 (95% confidence in terval 1.52-2.43). Conclusion. The familial component of RA is shown to extend beyond the nucl ear family, thus providing stronger evidence for a significant genetic comp onent to RA.