In the context of this review, heritable epigenetic influences are most relevant. One example of a classical, heritable epigenetic influence is imprinting. Imprinting conveys information from parent to child through mechanisms that include DNA methylation or histone acetylation. These mechanisms retain the primary DNA sequence but can dramatically alter function of specific genes. DNA methylation at CpG sequences in the promoter regions of genes can profoundly alter gene transcription. Since methylation during the course of maternal oocyte (or paternal sperm) development is key to this process, familial patterns of gender-specific transmission can provide evidence for this subset of heritable epigenetic influence. The modest quality of current family datasets for addiction renders them a relatively weak basis for any strong inferences concerning parent-of-origin effects. Nevertheless, there is no segregation data of which we are aware that supports strong parent-of-origin effects on substance dependence. Thus, while there are obvious and large roles for nonheritable “epigenetic” influences in the biology of addiction, there is no current compelling evidence that there are any strong effects of overall heritable “epigenetic” influences, as classically defined. We nevertheless need to be alert for such influences as we unravel effects of variants in specific genes.
