For FTO rs8050136, the random effects summary odds ratio yielded also a mere p = 0.015, as compared with the impressive Mantel-Haenszel p = 1.3×10−12 originally reported. Between-study heterogeneity is also very large (77%). Heterogeneity is visible even with plain data inspection, especially for the Wellcome Trust Case Control Consortium vs. Diabetes Genetics Initiative results (figure 1). Consistent with this strong signal of between-study heterogeneity, the Wellcome Trust investigators have indeed found that this variant is a susceptibility marker for increased body mass index and obesity [12]. Type 2 diabetes susceptibility may be mediated through the effect on body mass index and is not an independent effect that should have been seen consistently in all populations. The observed heterogeneity for type 2 diabetes association is also explained by the study design of the 3 GWA investigations. The Diabetes Genetics Initiative used a tightly matched case-control sample in the discovery phase, where cases and controls had been matched for body mass index [11] and thus it is not surprising that there was no residual effect of this FTO variant on the risk of type 2 diabetes.
