It is also important to note that even subtle methylation differences between individuals have been associated with variation in mRNA and protein levels (Bakulski et al., 2012; Huynh et al, 2014). From the data presented here, however, it is not yet clear what molecular effects are associated with the identified DMRs. Building on expression analysis from our previous publication (Szutorisz et al, 2014), we showed that several DMR-associated genes tested were also differentially expressed between THC and VEH groups. It is interesting to note that three genes containing hypermethylated DMRs showed mRNA overexpression in the cohort examined (Dlgap, Begain, and Kcna5), whereas one gene (Grin2a) was associated with both hypomethylation and decreased expression status; in all four cases, DMRs were located within gene bodies, in which effects of methylation are less clearly defined (Deaton and Bird, 2011). Large-scale assessment of the broader mechanistic relationships between DNA methylation variation within THC-associated DMRs and gene regulation will be the subject of future analyses.
