A genome-wide association scan for rheumatoid arthritis data by Hotelling's T(2 )tests

We performed a genome-wide association scan on the North American Rheumatoid Arthritis Consortium (NARAC) data using Hotelling's T(2 )tests, i.e., T(H )based on allele coding and T(G )based on genotype coding. The objective was to identify associations between single-nucleotide polymorphisms (SNPs) or markers and rheumatoid arthritis. In specific candidate gene regions, we evaluated the performance of Hotelling's T(2 )tests. Then Hotelling's T(2 )tests were used as a tool to identify new regions that contain SNPs showing strong associations with disease. As expected, the strongest association evidence was found in the region of the HLA-DRB1 locus on chromosome 6. In the region of the TRAF1-C5 genes, we identified two SNPs, rs2900180 and rs3761847, with the largest and the second largest T(H )and T(G )scores among all SNPs on chromosome 9. We also identified one SNP, rs2476601, in the region of the PTPN22 gene that had the largest T(H )score and the second largest T(G )score among all SNPs on chromosome 1. In addition, SNPs with the largest T(H )score on each chromosome were identified. These SNPs may be located in the regions of genes that have modest effects on rheumatoid arthritis. These regions deserve further investigation.