To examine whether ESAIMs could control for European population substructure in association testing the cases and controls from the NARAC RA studies were analyzed for selected SNPs. These analyses were performed using a set of individuals that did not include those used in the ESAIM selections. The SNPs for testing were selected based on our previous results to specifically address the effect of population substructure (Table 3). These included two gene associated SNPs that showed potential false positive results in our association tests, rs1446585 for lactase (LCT), and rs12203592 for interferon regulatory factor 4 (IRF4). In addition, a PTPN22, a TRAF1 and an MHC SNP were included in the testing as positive controls since these SNPs and gene loci are believed to be RA susceptibility genes based on our studies in European populations [23]. As a comparison to the ESAIMs, the same data was analyzed using the entire 500K SNP set with the EIGENSTRAT method.
