A systems omics-based approach to decode substance use disorders and neuroadaptations.

• MECP2 behaves as a master switch during substance use. • Five distinct gene clusters were identified based on addictive agents. • Another gene cluster is found central to addiction pathway. • Susceptible, methylated and acetylated genes interact among themselves. • PPARA from cannabis cluster regulates CHRNA2 in nicotine addiction. Substance use disorders (SUDs) are a group of neuropsychiatric conditions manifesting due to excessive dependence on potential drugs of abuse such as psychostimulants, opioids including prescription opioids, alcohol, inhalants, etc. Experimental studies have generated enormous data in the area of SUDs, but outcomes from such data have remained largely fragmented. In this review, we attempt to coalesce these data points providing an important first step towards our understanding of the etiology of SUDs. We propose and describe a 'core addictome' pathway that behaves central to all SUDs. Besides, we also have made some notable observations paving way for several hypotheses; MECP2 behaves as a master switch during substance use; five distinct gene clusters were identified based on respective substance addiction; a central cluster of genes serves as a hub of the addiction pathway connecting all other substance addiction clusters. In addition to describing these findings, we have emphasized the importance of some candidate genes that are of substantial interest for further investigation and serve as high-value targets for translational efforts. [ABSTRACT FROM AUTHOR]