If that were to be the case, then distinct variants at the SNCA and MAPT loci would be involved in a whole spectrum of disease-promoting mechanisms, i.e., from co-regulating overall susceptibility to PD at a site where gene–environment interactions occur, to participating in the ensuing tissue responses that propagate disease, and in doing so, to ultimately co-regulating the phenotypic expressivity of an α-synuclein-related disorder. The gene discussed is MAPT; the disease is Parkinson disease.