Results from genome-wide methylation studies of SUD generally do not replicate results from candidate gene methylation studies (Andersen, et al., 2015). Studies of chronic smoking using DNA methylation microarrays consistently report decreased DNA methylation in three locations that are involved in mechanisms outside of the CNS including cell signalling and platelet activation (cg05575921 in the the second exon of coagulation factor II receptor-like 3 gene, F2RL3), chronic inflammation (cg19859270 in the first exon of the G-protein-coupled receptor 15 gene, GPR15), and tumor suppression and cigarette toxin metabolism (cg05575921 in the third intron of the aryl hydrocarbon receptor repressor gene, AHRR). Results across genome-wide methylation studies of alcohol have not replicated. One study reported differential methylation at some sites that are involved in pathways related to alcohol metabolism (i.e., alcohol dehydrogenase and aldehyde dehydrogenase) as well as synaptic transmission (gamma-aminobutyric acid type A receptor pi subunit, GABRP). To date, there are no genome-wide methylation studies for cannabinoids or opioids (Andersen, et al., 2015).
