Although the STRUCTURE analysis was most consistent with two population groups explaining most of the substructure within Europe, the distribution of individuals from different countries of origin along the second axis in the PCA (Table 2; Figure 1B) suggested that further analysis of substructure was warranted. This substructure was examined using individuals of “northern” European ancestry in the context of a large dataset of rheumatoid arthritis cases and controls (over 2000 total individuals) that were recently genotyped with >500K SNPs as part of the NARAC studies (see Methods). For these PCA we examined only those European individuals that showed >90% membership in the northern European group by STRUCTURE analysis using the 1441 north/south-ESAIMs. This criterion closely matched the individual distribution along the first principal component axis of this dataset (Figure S3). Controlling for this first vector in analysis of cases vs. controls decreased the inflation of the median chi-square distribution using the genomic controls parameter (λgc) from 1.43 to 1.15.
