Genetics and Epigenetics of Alcohol Use Disorder

Alcohol is a commonly used addictive substance, and its chronic use can cause alcohol use disorder (AUD). AUD is a disability because cognitive impairments in individuals lead to a reduced ability to make decisions. The consumption of alcohol can result in falls or traffic accidents, which in turn can lead to reduced physical mobility. The susceptibility to AUD is thought to be the result of the complex relationship between environmental factors and individuals’ genetic predisposition. Genetic variations associated with AUD have been demonstrated to play a role in the development and maintenance of this disorder. Given that AUD is a polygenic disease, numerous gene variations have been linked to AUD in candidate gene association studies. The most commonly associated genes are those that encode the enzymes that metabolize alcohol including ADH and ALDH. Genetic variations in the genes encoding a multitude of neurotransmitters and receptors that play a pivotal role in the biological effects of alcohol are also associated with an increased risk of AUD. Nevertheless, genetic variations can only account for approximately 50% of the susceptibility to AUD. Exposure to alcohol, whether acute or chronic, results in epigenetic changes including histone modifications, DNA methylation, and noncoding RNAs, which alters gene expression and leads to differences between individuals. The identification of genetic variations and epigenetic changes that predispose to AUD is of paramount importance for the identification of candidate markers for AUD prognosis, diagnosis, and treatment. This chapter addresses the toxicokinetics and toxicodynamics of alcohol, the roles of polymorphisms in genes encoding enzymes, receptors, ion channels or neurotransmitters involved in these pathways in predisposition to AUD, and epigenetic alterations that are induced by acute or chronic alcohol consumption.