Little is known about how the genetic variation in vitamin D modulating genes influences ultraviolet (UV)B-induced 25-hydroxyvitamin D [25(OH)D] concentrations. In the Food with vitamin D (VitmaD) study, we showed that common genetic variants rs10741657 and rs10766197 in 25-hydroxylase (CYP2R1) and rs842999 and rs4588 in vitamin D binding protein (GC) predict 25(OH)D concentrations at late summer and after 6-mo consumption of cholecalciferol (vitamin D₃)-fortified bread and milk. In the current study, called the Vitamin D in genes (VitDgen) study, we analyzed associations between the increase in 25(OH)D concentrations after a given dose of artificial UVB irradiation and 25 single nucleotide polymorphisms located in or near genes involved in vitamin D synthesis, transport, activation, or degradation as previously described for the VitmaD study. Second, we aimed to determine whether the genetic variations in CYP2R1 and GC have similar effects on 25(OH)D concentrations after artificial UVB irradiation and supplementation by vitamin D₃-fortified bread and milk. The VitDgen study includes 92 healthy Danes who received 4 whole-body UVB treatments with a total dose of 6 or 7.5 standard erythema doses during a 10-d period in winter. The VitmaD study included 201 healthy Danish families who were given vitamin D₃-fortified bread and milk or placebo for 6 mo during the winter. After UVB treatments, rs10741657 in CYP2R1 and rs4588 in GC predicted UVB-induced 25(OH)D concentrations as previously shown in the VitmaD study. Compared with noncarriers, carriers of 4 risk alleles of rs10741657 and rs4588 had lowest concentrations and smallest increases in 25(OH)D concentrations after 4 UVB treatments and largest decreases in 25(OH)D concentrations after 6-mo consumption of vitamin D₃-fortified bread and milk. Common genetic variants in the CYP2R1 and GC genes modify 25(OH)D concentrations in the same manner after artificial UVB-induced vitamin D and consumption of vitamin D₃-fortified bread and milk.