We found strong evidence of association between low vitamin D levels and SNPs rs12785878 and rs4588, harboured by DHCR7 and GC, respectively, while only a non-significant trend was observed for rs10741657 at CYP2R1. More importantly, when the three SNPs were considered in a combined fashion as indicated by a genetic risk score, a very strong association with both serum vitamin D and hypovitaminosis was observed. This evidence concerns the gene CYP2R1 and vitamin deficiency.