Genomics and epigenomics of substance use disorders: An introduction

Abstract

Substance use disorders (SUD) are common conditions around the world, with important health and societal impacts, particularly in the burden of disease (disability-adjusted life years) (Whiteford, Ferrari, Degenhardt, Feigin, & Vos, 2015). The Global Burden of Disease Study estimated the global number of cases for SUD for several substances as follows: 94.8 million for alcohol, 17.2 million for amphetamine, 15.5 million for opioids, and 13.1 million for cannabis (Whiteford, 2015). In the United States, the lifetime and 12-month prevalences of SUD were 9.9% and 3.9%, respectively (Grant et al., 2016). In addition, polysubstance use is an important challenge in the field of addiction research (Whiteford et al., 2015).SUD are complex psychiatric disorders that result from the interaction of genetic, epigenetic, and environmental risk factors. Several studies have shown an important role for genetic factors in the etiology of major SUDs, with an estimated heritability of 65% for cocaine, 59% for nicotine, 51% for cannabis, and 50% for alcohol (Wang, Kapoor, & Goate, 2012). In the last decades, many candidate gene and genome-wide association studies (GWAS) have been performed to identify those genetic risk factors that underlie SUD, highlighting some relevant genes for the development of dependence on several drugs of abuse like alcohol (e.g., ADH1B, ADH2C, and ALDH2), nicotine (e.g., CHRNA5), and opioids (e.g., OPRM1) (recently reviewed by Lopez-Leon, Gonz alez-Giraldo, Wegman-Ostrosky, & Forero, 2021). Furthermore, some studies have started to identify genetic risk factors that are shared by several SUD and comorbid psychiatric disorders (Cabana-Domínguez, Shivalikanjli, Fernàndez-Castillo, & Cormand, 2019;Gurriar an et al., 2019). However, the genetic risk variants identified so far explain only a small fraction of the heritability of this complex disorder, and hence further studies and larger sample sizes are needed.Recent research has focused also on epigenetics to understand the interplay between environmental and genetic factors and druginduced changes involved in the remodeling of brain circuits and functional changes that underlie the transition from use to dependence.Repeated drug use has been shown to induce chromatin and histone modifications and alterations in DNA methylation that contribute to stable gene expression changes involved in these mechanisms, and that are also relevant for relapse in drug use (Beayno, El Hayek, Noufi,