There is substantial genetic and epidemiological
evidence implicating vitamin D in the pathogenesis of
many common diseases. A number of studies have sought
to define an association for disease with sequence variation
in the VDR gene, encoding the ligand-activated nuclear
hormone receptor for vitamin D. The results of such studies
have been difficult to replicate and are likely to need to
account for specific environmental exposures. Here, we
review recent work that has begun to study the interactions
between VDR gene polymorphisms, vitamin D blood levels,
and complex disease susceptibility, notably in the
context of major clinical outcomes. We highlight the
challenges moving forward in this area and its importance
for effective clinical translation of current research.