designs and a variety of populations in order to capture more robust signals. Of note, supplemental network and pathway analyses may be useful even in the absence of highly significant findings in order to elucidate the underlying biology of chronic substance exposure if they point toward relevant underlying biological pathways. Below, we highlight several guidelines to consider when designing such studies, based on the results of our review, in order to maximize the chances of finding epigenetic biomarkers for substance use disorders, while also addressing issues of replicability, generalizability, and cost. We will also address challenges in the design and interpretation of such studies, and acknowledge important limitations of the current literature.
