Whole-Exome Sequencing of Diverse Populations

In total, 3862 samples were selected for whole-exome sequencing from a larger data set of 8214 samples previously genotyped with the OMNI 2.5 array (Illumina).^{4 (link)} To increase representation of genetic variation not queried in studies of European populations, selection criteria for whole-exome sequencing was based on the proportion of Native American ancestry estimated from principal component analysis of genotype data (eMethods section and eFigures 1 and 2 in the Supplement). Whole-exome sequencing was performed on blood DNA from these samples using Sure-Select Human All Exonv2.0(Illumina),44-Mb–baited target. Raw reads were mapped with the Burrows-Wheeler Aligner, reprocessed with Picard to recalibrate base quality scores and perform local realignment around known indels. Genetic variants were called with the Genome Analysis Toolkit Unified Genotyper module^{14 (link)} and were filtered to remove likely artifacts using several quality-control metrics such as mean coverage, concordance of nonreference genotypes with array data, and missing rate as specified in the eMethods section in the Supplement. Independent replication was sought in whole-exome sequence data from the T2D-GENES and GoT2D projects, which together sequenced 13 098 individuals from 5 ethnic groups (Europeans, East Asians, African Americans, South Asians, and Latinos).