Omni 2.5 array

Study participants in the Mexico City Diabetes Study, as well as
genotyping using the Illumina OMNI2.5 array and exome-sequencing, have been
previously described (Estrada et al.,
2014; Williams et al.,
2014). Informed consent was obtained from all subjects, and the
study was approved by the Comité de Etica e Investigatión
committee at The Centro de Estudios en Diabetes. In sum, plasma from a total
of 677 individuals with genotyping, including 364 carriers of the
SLC16A11 risk haplotype (mean age 52.6 ± 7.6;
40.4 % male) and 313 controls (mean age 52.6 ± 7.6; 37.4 % male),
underwent lipid profiling as described below. No individuals at the time of
lipid profiling had type 2 diabetes. An analysis of the influence of sex on
the association between SLC16A11 status and TAG pattern was
not performed because sex is not known to influence the association between
SLC16A11 status and diabetes risk

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).

Genotyping of study participants using the Illumina OMNI2.5 array (Williams et al., 2014 (link)) and exome-sequencing (Estrada et al., 2014 (link)) have been described previously. The Genomics Platform at the Broad Institute (Cambridge, MA) received, quality controlled, and tracked DNA samples, and carried out exome array processing. The samples were plated into 96-well plates that included a quality control sample for processing on the Illumina HumanExome BeadChip (Illumina, Inc. San Diego, CA) using manufacturer’s protocols. The arrays were scanned using Illumina iScans.
Genotypes were called using Birdsuite (https://www.broadinstitute.org/birdsuite/birdsuite). Clusters were fit using the Birdseed algorithm to each genotyping plate independently. Genotypes with confidence below 99.9% were excluded from analysis (e.g. considered “missing” or “no-call” genotypes). Samples with low numbers of non-reference alleles (< ~20,000, depending on the cohort), low call rate (<99.3%) or unusually high heterozygosity (> ~0.05, depending on the cohort) were removed from subsequent analysis; thresholds were chosen based on visual inspection of the sample distributions. Variants with low call rate (<99.2%) or mean confidence for alternative genotype calls (<99%) were also excluded from subsequent analysis.