PCA of the “north” only subset showed substantial substructure differences in the distribution of North American Rheumatoid Arthritis (NARAC) cases and controls along the first PC (Figure 4). Importantly, we controlled for this difference in our genome-wide association scan and excluded SNPs that showed association based on this substructure difference [23]. The distribution of individuals in this PC showed a distinct pattern with respect to the context of country of origin information that was available for a subset of control individuals (Figure 4B). Most notably, Irish individuals were distinguished from those of eastern, northern and central European descent. These relationships were further defined by inclusion of additional individuals with the same country of origin genotyped with the 300K SNP set (Table 2). Similar results were also observed using a STRUCTURE analysis of the same dataset (Table 2). The results suggest that the difference in numbers of individuals of Irish ancestry was primarily responsible for the major difference in substructure observed in the NARAC cases and controls [23]. Controlling for this aspect of substructure the λgc in this individual set decreased
