One- and two-locus models for mapping rheumatoid arthritis-susceptibility genes on chromosome 6

To evaluate whether there is evidence for two rheumatoid arthritis (RA) susceptibility genes on chromosome 6, we applied new robust methods for two-locus multipoint identical-by-descent mapping to the rheumatoid arthritis data of the Genetic Analysis Workshop 15. The software GEEARP was used to estimate the locations and the corresponding genetic effects for one locus or two linked loci in a region on chromosome 6, on the basis of affected relative pairs. These methods were applied to the data sets from the North American Rheumatoid Arthritis Consortium, Canada, France, and the first screen of United Kingdom. From the resultant 95% confidence intervals given by a robust variance estimator, a linked region, other than the well-known HLA region, was at 54.7–69.6 cM, providing evidence for a second rheumatoid arthritis susceptibility locus on chromosome 6.