and consequence of chronic substance use. Animal research shows that repeated drug use alters gene expression profiles in the brain reward system, through epigenetic mechanisms such as histone acetylation and methylation change (see Renthal and Nestler,132 Maze and Nestler133 and Wong et al.134 for reviews) and there is no doubt that epigenetic variation is an integral component of the biology of addiction. Although epigenomic methodologies (for example, whole genome methylation) grow increasingly accessible, the primary challenge remains tissue-specificity: epigenetic signatures in peripheral tissues (for example, leukocytes) may not correlate with those in the central nervous system. This has led to increasing investment in the NIH Roadmap Epigenomics Project,135 which aims to develop databases of human epigenomic maps (epigenome atlas) in a variety of healthy and tumor tissue and eventually, to provide a degree of cross-tissue correspondence in epigenomic profiles. Even in the absence of direct epigenomic typing, resources such as the Encyclopedia of DNA Elements136 allow flexible annotation of the functional landscape of the human genome, such as regions of potential epigenomic modification.
