Alcoholism and Genetics: Is Addiction Hereditary?

To understand the genetics behind alcoholism, it helps to have a basic understanding of the difference between the terms used in research. The terms genetic and hereditary are often used interchangeably; however, this is technically incorrect. A genetic disease is always caused by an abnormality in a person’s genome, although some of these diseases are hereditary. Genetic diseases can range from a discrete mutation in a single base in the DNA of a single gene–to a gross chromosome abnormality involving the addition or subtraction of an entire chromosome or set of chromosomes. A genetic predisposition or susceptibility increases an individual’s risk of developing a particular disease based on their genetic makeup. An individual with a hereditary disease has inherited the gene mutation from their parents.

The Alarming Scope of Alcoholism

In 2016, an estimated 15.1 million people aged 12 and older had an alcohol use disorder (AUD) and 65.3 million and 16.3 million people aged 12 or older were past-month binge and heavy alcohol users, respectively. Alcohol is associated with an estimated 88,000 deaths per year in the U.S. and $249 billion in economic costs. Given the enormous physical, psychological and economic impact alcohol imparts on individuals, loved ones and society as a whole, research is crucial. Understanding whether alcoholism stems from a larger set of inherited genes or mutations in select genes and/or other contributing factors is important for prevention, advances in treatment (e.g. new pharmaceuticals) and potential cures.

The Genetics of Addiction

Genetics is deeply entwined with the evidenced-based concept addiction is a chronic brain disease. Although scientists assert 40-60% of the risk for addiction is genetic, recent investigations suggest the interplay of a large number of causal risk variants each contribute relatively small effects. The complex set of phenotypes and genotypes potentially involved in addiction presents a formidable research challenge.

Alcoholism Research: Genetics and Heredity

The most common focus of alcohol studies are well-established neurotransmitter systems commonly studied in psychiatric disorders such as dopamine, serotonin and glutamate and their receptors, transporters and enzymes of degradation. The second most common area of research is specialized neurotransmitters such as vasopressin and orexin. A third common theme is genes related to one carbon metabolism. And the fourth and fifth common areas of study are genes related to craving, especially those associated with the opioid system or neuronal growth and homeostasis. Family studies indicate children of parents with high-risk alcohol dependence are at much greater risk of developing alcohol problems. Twin studies have consistently shown substance initiation is significantly influenced by genetic, as well as shared and unique environmental factors. Research also suggests stressful environmental exposures during childhood increase the risk of alcohol dependence. In overall terms, alcohol research has found drinking frequency, binge drinking, alcohol abuse or dependence all have familial elements and are moderately heritable. Although significant genetic associations of hundreds of markers have been linked to AUD, it has been difficult to consistently replicate these associations across studies. Research indicates decreased D2-like dopamine receptor expression is associated with an increased risk of AUD. Preliminary evidence implies a simple mutation (variation in a single base pair in a DNA sequence) in the pre-proghrelin gene (GHRL) and the gene responsible for the production of the ghrelin receptor (GHSR-1a) are associated with increased alcohol use. Some studies have analyzed the potential role of gene variants in alcohol methylation. Unfortunately, in addition to the inconsistency of results, global methylation is unlikely to translate as a biomarker for alcohol use due to its lack of specificity. A 2014 study published in Nature uncovered nearly a dozen genes strongly implicated in alcoholism, with SNCA (synuclein alpha) the number one candidate. This gene has been reported to be involved in modulating brain plasticity and neurogenesis, as well as neurotransmission, primarily as a brake. Low levels of SNCA may offer less protection against oxidative stress, whereas high levels of SNCA may have a role in neurodegenerative diseases, including Parkinson’s disease. SNCA has been identified as a susceptibility gene for alcohol cravings and response to alcohol triggers. Evidence from this study and others suggest a genetic rather than purely environmental (alcohol consumption and stress) basis for SNCA alteration, and its potential utility as a trait rather than purely a marker. Researchers concluded anxiety, mood and cognition, precipitated by environmental stress and genetic vulnerability can all help determine the course of alcoholism.

Can a Genetic Foundation of Alcoholism Reduce Stigma?

In a 2017 study on 63 participants, one-third believed confirmation of a genetic predisposition would help them accept and embrace treatment for their addiction and cope with associated guilt. Yet, the majority of participants did not believe specific genetic information would be useful to their recovery. The most common reason was that regardless of the cause, they had to do the hard work to maintain abstinence. Even so, those being treated for alcoholism said that if they knew they were genetically inclined to addiction, they would be more likely to seek treatment and never drink again. The vast majority of individuals believed a genetic framework would foster sympathy towards individuals who have the “genetic disease” of addiction. This could positively impact treatment rates since stigma is still a serious barrier to seeking alcoholism treatment. Researchers hope a better understanding of the biological mechanisms and role of gene mutations may facilitate the development of improved biomarker-based approaches to personalize substance abuse treatment.