In combining the 3 GWA scans, several challenges were encountered and analytically overcome. The 3 studies had been carried out on different genotyping platforms. To overcome this, SNPs were imputed across the HapMap, and this allowed maximized use of the information available. The scans had different ascertainment schemes, for example in terms of matching cases and controls for BMI, a known T2D risk factor. To address this, both fixed- and random effects meta-analyses were carried out and evidence for informative heterogeneity was examined. One prime example of informative heterogeneity is the FTO locus, the first robustly replicating obesity susceptibility locus [47], which was associated with T2D in some, but not other scans. In particular, this locus did not achieve significant evidence for association with T2D in scans that had matched cases and controls for BMI.
