Some heterogeneity in cross-study results is anticipated and it may be attributable to biases in the collection of exposure data, phenotype definition, participant selection, population structure, and various elements of the genotyping process [Ioannidis et al., 2007; Nakaoka and Inoue, 2009]. GENEVA’s refined genotyping QC protocol should safeguard against some of these biases, but those pertaining to cross-study differences in study design will require special attention and are, therefore, addressed by individual phenotype harmonization working groups. Heterogeneity may also reflect genuine differences such as LD structure or environmental exposure diversity across populations [Nakaoka and Inoue, 2009]. The former may assist in pinpointing the causal variant and the latter may lead to hypothesis generation, complementing those already proposed by GENEVA investigators and those that might be pursued either within or outside the consortium. Thus, despite the challenges GENEVA anticipates through cross-study analyses, results should generate a new insight into the gene-trait association.
