There are many reasons that can underlie heterogeneity [29]. Besides heterogeneity due to chance, we still have limited insight into how much heterogeneity may be due to errors and biases differently affecting the results of different datasets, or to what extent heterogeneity may represent genuine differences in genetic effects across different populations and different biological setting, i.e. truly informative heterogeneity [30,31]. Informative heterogeneity may reveal interesting facts about biology, e.g. the mechanism through which the variant is acting on disease risk. One has to be cautious to avoid discarding such associations as replication failures. Heterogeneity could also result from the presence of variable LD between the typed marker and the causal variant.
