Genetics and genomics of alcohol sensitivity

Abstract

Alcohol abuse and alcoholism incur a heavy socioeconomic cost in many countries. Both genetic and environmental factors contribute to variation in the inebriating effects of alcohol and alcohol addiction among individuals within and across populations. From a genetics perspective, alcohol sensitivity is a quantitative trait determined by the cumulative effects of multiple segregating genes and their interactions with the environment. This review summarizes insights from model organisms as well as human populations that represent our current understanding of the genetic and genomic underpinnings that govern alcohol metabolism and the sedative and addictive effects of alcohol on the nervous system.Electronic supplementary materialThe online version of this article (doi:10.1007/s00438-013-0808-y) contains supplementary material, which is available to authorized users.

Genetics of alcohol consumption in Drosophila melanogaster

“…RAP1GAP has been associated with prostate (Bailey et al , 2009) and gastric cancers (Yang et al , 2016). EGFR and YWHAB have been previously mapped to genetic network for alcohol-related phenotypes (Morozova et al , 2014). …”

Strain-specific programming of prenatal ethanol exposure across generations

“…Subsequently, such epigenetic modifications may be transmitted from the F1 to F2 generation as previously described (Anway et al, 2005, Pfinder et al, 2014). Sensitivity to alcohol is a quantitative and qualitative trait that is determined by a complex integration of several genes (genetics) and their interaction with the environment (epigenetics) (Morozova et al, 2014). Approximately 30% to 70% of vulnerability to drug abuse is genetically heritable (Goldman et al, 2005), while environmental factors account for the rest (Renthal and Nestler, 2008), supposedly through epigenetic mechanisms., Therefore, both genetic and epigenetic factors may contribute to the strain-differences in vulnerability to PAE and ethanol-induced hypnosis between Long Evans and Sprague Dawley strains.…”

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

“…Clinical and basic research indicate that 1) lower responsivity to ethanol’s effects is directly associated with alcohol abuse and dependence (e.g., Crabbe, Bell & Ehlers, 2010; Draski & Deitrich, 1996; Heit et al, 2013; Morean & Corbin, 2010; Morozova, Mackay & Anholt, 2014; Schuckit & Gold, 1988; Silveri, 2012, 2015; Spear, 2010, 2014); 2) the ability to display greater levels and quicker development of tolerance (a reduction in ethanol’s effects after prior treatment with ethanol) to ethanol’s effects is also associated with alcohol abuse and dependence (e.g., Lê & Mayer, 1996); 3) additionally, the expression of anxiety-like behavior under basal and/or withdrawal conditions is associated with a propensity to abuse alcohol (e.g., Heilig, Egli, Crabbe, & Becker, 2010; Heilig, Thorsell, et al, 2010; Kirby, Zeeb, & Winstanley, 2011; Pautassi, Camarini, Quadros, Miczek, & Israel, 2010; Thorsell, 2010); and 4) moreover, the expression of low- to moderate-dose ethanol-induced stimulation [which is modeled in rodents by increased motor activity/approach behavior (Chappell & Weiner, 2008; Faria et al, 2008; Wise & Bozarth, 1987), aggression (Chiavegatto, Quadros, Ambar, & Miczek, 2010), and social facilitation (Varlinskaya & Spear, 2009, 2010)] is associated with excessive alcohol consumption. This behavioral phenotype may have pharmacological validity as well, such that the histaminergic (c.f., Panula & Nuutinen, 2011 and references therein) and ghrelin (c.f., Jerlhag, Landgren, Egecioglu, Dickson, & Engel, 2011b and references therein) systems have been implicated in ethanol-induced motor activation, ethanol-induced conditioned place preference, alcohol-preference and high alcohol consumption behavior.…”