Understanding the disorder-specific role of intragenic DNA methylation is critically important,40, 41 providing a unique opportunity to investigate gene/environment interactions of clinical significance.42 In this study, highly significant relationships were found between the intragenic methylation within the 5′ end of the FMR1 intron 1 and phenotype measures of executive function, volume of white matter hypointensities and regional cortical thickness in the frontal and parietal cortices of PM females without FXTAS. The gene discussed is FMR1; the disease is fragile X-associated tremor/ataxia syndrome.