A Brief History of Research on the Genetics of Alcohol and Other Drug Use Disorders

Abstract

ABSTRACT. Objective: This article reviews developments in research on genetic infl uences on alcohol and other drug use and disorders over the past 7 decades. Method: The author began with a review of the fl ow and content of articles published in the three iterations of the journal since 1940 and then used a PubMed search of genetics of alcohol and other drug-related topics to gain a broad overview of developments in this fi eld. Results: The literature demonstrates the rapid metamorphosis of genetic research from the ideas of Mendel to an understanding that the substance use disorders are complex, genetically infl uenced conditions where genes explain up to 60% of the picture. Most genes operate through additional intermediate characteristics, such as impulsivity and a low sensitivity to alcohol, some of which are substance specifi c and others related to substances in general. Using linkage, association, genome-wide association, and other modern methods, investigators have identifi ed a diverse range of genetic variations that affect substancerelated phenomena. Conclusions: Genetic studies regarding alcohol and other drug use and problems have grown dramatically in the past 75 years. We currently have a much more sophisticated understanding of these infl uences, and the rapid development of new methods has the promise of continuing what has been a solid contribution of important fi ndings in recent years. (J. Stud. Alcohol Drugs, Supplement 17, 59-67, 2014)

The Low Level of Response to Alcohol-Based Heavy Drinking Prevention Program: One-Year Follow-Up

“…The goals were to modify well-established components of campus-based prevention programs often used to help students decrease heavy drinking (e.g., Borsari & Carey, 2001;Carey et al, 2007;Larimer & Cronce, 2007) in order to address a specifi c genetically infl uenced preexisting risk factor for excessive alcohol intake-the low LR to alcohol (Schuckit, 2014)-as well as to deliver the information on the Internet. The latter is important because the Internet has proven to be useful, effective, and relatively inexpensive in school-based prevention programs (Champion et al, 2013).…”

“…Genetic infl uences explain more than 50% of the risk for heavy drinking and alcohol problems and operate through intermediate characteristics such as impulsivity and a person's alcohol response (King et al, 2014;Newlin & Renton, 2010;Schuckit, 2014). The latter includes low levels of response (low LRs), which is observed predominantly for sedating effects of alcohol at peak and falling blood alcohol concentrations.…”

“…Once people vulnerable to alcohol problems are found, working with them to alter environmental mediators of their predisposition may be more likely to change behaviors and carry fewer risks than modifying the large number of genes likely to contribute to these conditions (Schuckit, 2014). Our group has identifi ed several mediators of how a low LR enhances problematic drinking, including selecting heavier drinking peers who reinforce high consumption, developing expectations that drunkenness is desirable, experiencing higher stress related to heavy drinking, and using alcohol to cope with stress (Borsari & Carey, 2001, 2003Fromme & D'Amico, 2000;Patrick et al, 2010;Schuckit et al, 2011b;Veenstra et al, 2007).…”

“…The overall goals were to modify well-established components of campus-based prevention programs (e.g., Borsari & Carey, 2001;Carey et al, 2007;Larimer & Cronce, 2007) to address a specifi c genetically infl uenced preexisting risk factor for excessive alcohol intake (Schuckit, 2014). The fi rst step was a pilot study of 64 drinking but not alcohol-dependent freshmen who were selected as high and low LR pairs based on a median split on the Self-Rating of the Effects of Alcohol (SRE) questionnaire (Schuckit et al, 2012).…”

The Impact of Focusing a Program to Prevent Heavier Drinking on a Pre‐existing Phenotype, the Low Level of Response to Alcohol

“…Generally, males are more likely to have alcohol problems than females (Barnett et al, 2014; Polak and Conner, 2012), and European Americans (EA) and Hispanics consume more alcohol than African Americans (AA) and Asians (Barnett et al, 2014; Eng et al, 2007; Li et al, 2011; Wu et al, 2011). Heavy drinking and associated problems also relate to several aspects of a person's response to alcohol (King et al, 2014; Newlin and Renton, 2010; Schuckit, 2014), including the need for higher blood alcohol concentrations (BACs) to produce a range of effects (Low level of Response, or Low LR, to alcohol) (Quinn and Fromme, 2011; Schuckit et al, 2011a). Low LR best predicts future higher quantities per occasion, with less impact on drinking frequencies (Chung and Martin, 2009; Quinn and Fromme, 2011; Schuckit et al, 2011b, 2012b, 2014; Scott, 2012).…”