Genome-wide linkage and association analysis of rheumatoid arthritis in a Canadian population

Rheumatoid arthritis (RA) is an autoimmune disease with a moderately strong genetic component. Previous linkage and candidate gene studies have identified several regions that predispose to RA, including the HLA-DRB1 and PTPN22. We conducted genome-wide linkage analysis with 128 affected individuals from 60 families in a Canadian cohort that were genotyped using the Illumina linkage panel and genome-wide association analysis with 158 affected individuals from the same cohort that were genotyped using the Affymetrix 100 K platform. Multipoint nonparametric linkage scan revealed three linkage peaks with LOD scores greater than 1.5. We also identified 13 significantly associated SNPs at the genome-wide level of 0.05 after Bonferroni adjustment for multiple testing. Several of the significantly associated SNPs are located close to previously identified linkage regions, but not in the linkage peaks identified in the same cohort. We could not replicate association with HLA-DRB1 and PTPN22. Our results indicate that high coverage and sufficient sample size are crucial for the success of genome-wide association studies.