The Val350Val homozygote could not be observed or showed extremely low frequency in Asian and African American samples (but not in Europeans or Native Americans), thus, the analysis under the recessive model (ValVal vs. ValIle + IleIle) tended to produce a wider CI compared to that under the dominant model. On the other hand, despite the stringent criteria that were applied in the selection of studies, the samples in some studies might not be entirely random because the participants might have been screened for certain alcohol-related medical conditions. In addition, Hardy-Weinberg disequilibrium in patients or controls may support that the gene is related to AD, however, disequilibrium in controls may also reflect genotyping error and thus potentially reduce the powerof the analysis (however, of the control samples that were not in equilibrium, either the samples were small or the disequilibrium was not highly significant considering our strong findings).
