Another factor raising concerns regards the reversed replication results of the set of hits on 6p21.32, near HLA-DRA gene. A possible explanation may lie in the high gene density and polymorphism rate of the HLA region, combined with the lack of power in this study. The MAF investigation of the eight variants, including the HapMap-CEU population sample, revealed considerable MAF variance for the HLA-DRA variants, but not for the variants on 6p21.2, near to the LINC00951 gene. The only variant in the HLA-DR region on 6p21.32 showing similar MAF in discovery and replication was rs2395163 that tagged a relatively rare HLA-DRB1*04:04 association. As the allele frequency of HLA-DRB1*04:04 was only 0.04, it was not surprising that the association was not replicated in the relatively small replication sample. However, it is important to emphasize that the HLA-findings emerge only from the imputed GWAS data, and no replication was addressed in this study.
