For genetic analyses, S4S subjects were empirically assigned to 1KGP based ancestry super-populations. Briefly, using all 10 ancestry PCs, the Mahalanobis distance (Mahalanobis, 1936) between each S4S sample and each 1KGP population (N = 26) without reference population outliers (>4 SD from population median, N = 61) was calculated. Each subject was then assigned to the 1KGP population with the minimum Mahalanobis distance and then collapsed into their respective super-population assignment. This empirically based ancestry has several advantages to self-identified race/ethnicity including reducing variance of the within group PCs and being able to include “Unknown,” “More than one race,” and small groups in the analysis without an increase in genomic inflation. There were five final ancestry groups: African descent (AFR), American descent (AMR), East Asian descent (EAS), European descent (EUR), and South Asian descent (SAS).
