A fundamental principle in meta-analysis is that all studies included examined the same hypothesis. As such, the general design of each included study should be similar, and the study-level SNP analysis should follow near-identical procedures across all studies (see Zeggini and Ioannidis [47] for an excellent review). Quality control procedures that determine which SNPs are included from each site should be standardized, along with any covariate adjustments, and the measurement of clinical covariates and phenotypes should be consistent across multiple sites. The sample sets across all studies should be independent – an assumption that should always be examined as investigators often contribute the same samples to multiple studies. Also, an extremely important and somewhat bothersome logistical matter is ensuring that all studies report results relative to a common genomic build and reference allele. If one study reports its results relative to allele and another relative to allele , the meta-analysis result for this SNP may be non-significant because the effects of the two studies nullify each other.
