Multi-dimensional scaling (MDS) analysis was used to exclude duplicate and related samples as well as samples of non-European descent (other than the CVCR/ANT samples, which were set aside for subpopulation-specific QC) (Figure S3). Remaining EU and European-derived isolate samples were separated into three strata (EU, AJ and FC) based on observed genetic ancestry and source population (Figures S4-S6). Within each of the MDS-defined genetic subpopulations, additional outliers were removed for excess low-level relatedness, abnormal average heterozygosity or inadequate case-control matching. The final European ancestry sample contained 1285 cases and 4964 controls (EU: 778 cases, 4414 controls; AJ: 242 cases, 354 controls; FC: 265 cases, 196 controls) (Table 1; Figure S1). The final CVCR/ANT sample consisted of 211 cases (87 ANT, 124 CVCR) and 285 ANT controls.
