This method presumes that the mechanism of action for functional genetic variants is shared in common across human populations, although differences in allele frequencies at risk loci can lead to differences in prevalence. This premise is supported by an empirical study by Ioannidis et al. that showed that while the frequency of genetic markers may vary across populations (58% showed large heterogeneity), their biological impact on the risk for common diseases appears to be usually consistent across different 'races' (only 14% showed large heterogeneity in the genetic effects) [21]. Our analysis, which has demonstrated successful filtering of some of the SNPs correlated in the EA population, raises the interesting possibility that among these 14% of markers observed by Ioannidis to have heterogeneity of genetic effect, some fraction may still indeed correspond to gene variants that do have similar biological mechanism and genetic effect, but were represented by a SNP merely in LD with the true causal variant. Thus the proportion of common diseases for which the biological effects of the causative genetic variants are consistent across traditional racial groupings may perhaps be even higher than estimated in [21].
