Axiom chip

The Genomic Core Lab quantitated all samples by Pico Green (Thermo Fisher, Pittsburgh, PA) and diluted the DNA to 23ng/ul and shipped the plates on dry ice to Affymetrix (Los Angeles, CA) for genotyping. Plates also contained randomized duplicates. Affymetrix confirmed all DNA concentrations by Pico Green assay prior to genotyping. Genotyping used a custom designed Axiom® chip (see SNP selection below), and was performed using the Affymetrix GeneTitan® system as described in the axiom user manual⁵⁴ with resultant genotype calls provided for QC and analysis.

Genotyping for 3409 Caucasians was performed on two platforms: 1919 individuals using the Affymetrix Axiom chip as part of a previous study in nondiabetic CATHGEN patients [31 (link)] and 2300 using the Illumina Human Omni1-Quad Bead Chip. Two individuals failed quality control (call rate > 99% for both platforms) and four individuals were excluded because they were genotyped on both platforms but had discordant genotypes, resulting in 3403 unique individuals (Figure 1). Hardy–Weinberg Equilibrium for rs4149056 and rs2306283 was checked using PLINK, Version 1.07 [32 (link),33 ]. Genotypes were coded to test an additive model, based on prior observations supporting this relationship [34 (link)], defined as 0, 1, or 2 copies of the minor allele. Haplotypes (*1a, *1b, *5 and *15) were constructed from the two genotypes such that the *1a haplotype was designated the reference (i.e., N130, V174).