Research in epigenetic biomarkers for smoking encompasses three main waves of findings. First, many studies examined candidate genes such as Monoamine Oxidase A and B (MAO-A, MAO-B), often using bisulfite pyrosequencing techniques available in the 2000s to investigate the relationship between methylation at CpG islands and substance use disorders. Second, with the advent of array-based methylation detection technologies, a number of studies in varying populations, tissues, and sample sizes have been done. With the further development of arrays by Illumina and others, these studies have been able to expand from a limited number of CpG sites across the genome, generally focused in areas related to cancer, to a much broader range of sites. Third, based on the results of array-based studies, follow-up studies of promising loci have been done to more carefully delineate methylation patterns associated with smoking and investigate potential utility as biomarkers for smoking and related health risks. As it will be demonstrated in the rest of this review, this trajectory places smoking epigenetic biomarkers closest to translation into clinical practice, while other substance use disorders under study remain less developed.
