Conditional analysis of the major histocompatibility complex in rheumatoid arthritisReport as inadecuate

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BMC Proceedings

, 3:S36

First Online: 15 December 2009DOI: 10.1186-1753-6561-3-S7-S36

Cite this article as: Taylor, K.E. & Criswell, L.A. BMC Proc 2009 3Suppl 7: S36. doi:10.1186-1753-6561-3-S7-S36


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 × 10 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.

List of abbreviations usedLDLinkage disequilibrium

MAFMinor allele frequency

MHCMajor histocompatibility complex

NARACNorth American Rheumatoid Arthritis Consortium

OROdds ratio

PCAPrincipal components analysis

RARheumatoid arthritis

SEShared epitope

SNPSingle-nucleotide polymorphism

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Author: Kimberly E Taylor - Lindsey A Criswell


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