Multilocus analysis of GAW15 NARAC chromosome 18 case-control data

The Genetic Analysis Workshop 15 rheumatoid arthritis data included a set of 460 cases and 460 controls genotyped at 2300 closely spaced markers on a 10 megabase region of chromosome 18q. We conducted a multilocus analysis of these data using a localized haplotype clustering method that adapts to linkage disequilibrium structure and can be applied to large, densely genotyped data sets such as this one. We found a protective haplotype carried by 33 individuals that was significantly associated with rheumatoid arthritis in these data after adjusting for multiple testing. This haplotype was located less than 500 base pairs upstream of the CCBE1 gene. The association was not detected using single-marker tests, but could be found using a variety of multilocus tests.