In conclusion, we demonstrated that heterogeneity can have a major impact on GWAS findings. The extent of its effect is of large magnitude and, unexpectedly, affects significantly even loci robustly associated with the trait under study. We showed that even a relatively low proportion of “non cases” (20%) can dilute the observed genetic effect size for common variants (with MAF>0.05) targeted in the current GWAS analyses. The partial failure of GWAS to detect a substantial proportion of the heritability of genetic complex diseases could be a consequence of the presence of a high degree of heterogeneity.
