Conditional analysis of the major histocompatibility complex in rheumatoid arthritis.
We performed a whole-genome association study of rheumatoid arthritis susceptibility using Illumina 550k single-nucleotide polymorphism (SNP) genotypes of 868 cases and 1194 controls from the North American Rheumatoid Arthritis Consortium (NARAC). Structured association analysis with adjustment for potential population stratification yielded 200 SNPs with p < 1 x 10-8 for association with RA, all of which were on chromosome 6 in a 2.7-Mb region of the major histocompatibility complex (MHC). Given the extensive linkage equilibrium in the region and known risk of HLA-DRB1 alleles, we then applied conditional analyses to ascertain independent signals for RA susceptibility among these 200 candidate SNPs. Conditional analyses incorporating risk categories of the HLA-DRB1 "shared epitope" revealed three SNPs having independent associations with RA (conditional p < 0.001). This supports the presence of significant effects on RA susceptibility in the MHC in addition to the shared epitope.
Taylor
Kimberly E
KE
The Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, 374 Parnassus Ave, San Francisco, California 94143 USA. kim.taylor@ucsf.edu.
Criswell
Lindsey A
LA