Third, in order to address generalizability of findings, we will focus on research in human subjects rather than animal or in vitro models. Similarly, research in different ethnic groups, ages, and sexes will be included. The majority of research in substance use epigenetics has been in adults of European ancestry, but a few studies have included other ethnic groups and ages for comparison. In addition, when studies report differential findings by sex, these will be included in the review. These are particularly important aspects as studies have reported differences in global methylation in different sexes and ethnicities [31]. In addition to demographic aspects of study design, temporal aspects such as the measurement of changes in individuals or groups over time prospectively lend important additional aspects to clinical generalizability and may contribute to understanding of the underlying etiology of substance use disorders.
