Is Alcoholism Genetic Or a Choice?

Alcoholism

 

Is alcoholism in my genes, or in my control?

The nature vs. nurture question is an important, yet complicated one, for any sort of health condition.  Whether you are the one suffering, related to someone suffering, or simply interested in the development of conditions, we all want to know why we are the way we are. 

To get this out of the way, alcoholism isn’t entirely from genetic factors nor is it entirely due to environmental causes.  As with many other diseases, such as Alzheimer’s, diabetes, and depression, there are genetic and environmental roots.

 

The Genetics of Alcoholism:

 

Before going any further, defining alcoholism makes sense.

The DSM (Diagnostic and Statistical Manual of Mental Disorders) actually recognizes what we know as alcoholism as alcohol use disorder (AUD).

While the DSM lists 11 criteria for the diagnosis of AUD, we’ll go ahead and define alcoholism as this:  the persistent craving for alcohol, and the inability to function in everyday life/relationships as a result of drinking.

To be clear, there is no “alcoholism” gene.  While certain combinations of genes are closely associated with alcoholism, no one gene will determine your fate with the bottle.

The countless studies done on alcoholism suggest that hundreds of variants across the genome, most of small effect (R2 < 0.002), contribute to the genetic foundation of alcoholism.  We’ll discuss some of these in detail.

 

Metabolizing Alcohol

 

To understand the genetics of alcoholism, you need to understand how alcohol “passes” through the body.

Alcohol is first metabolized in the liver (in stomach and GI tract to lesser extents, too).  The ethanol is first oxidized (combined with oxygen) to acetaldehyde.  This reaction is mostly catalyzed by ADH’s.  There are 7 closely related ADHs clustered on chromosome 4.  As we’ll discuss, different ADH’s give individuals different ethanol metabolisms, and thus impact your likelihood of alcoholism.

Next, the acetaldehyde is metabolized to acetate by ALDH’s.  Like ADH’s, there are many ALDH’s, though ALDH2 has the largest impact on alcohol consumption (1).  In simplest terms, the ALDH’s determine, at least in part, your genetic potential for alcoholism.

 

Different Gene, Different Metabolism

 

The genes with the clearest contribution to risk for alcoholism are alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2; mitochondrial aldehyde dehydrogenase), two genes central to the metabolism of alcohol (ethanol).

ALDH2

Research shows that “even a single copy of the ALDH2*504K (ALDH2*2 allele; rs671) makes people with the gee display the “Asian flushing reaction” when they consume even small amounts of alcohol” (2).

As a result, drinking for these individuals causes facial flushing, nausea, and rapid heart beat.  These symptoms reduce their likelihood of developing alcoholism. 

ADH1B

The enzymes encoded by ADH1B*48His and ADH1B*370Cys “metabolize ethanol in vitro at 30-40-fold higher rates than does β1–ADH” (3-4).

In simplest terms, individuals with the above genes have higher metabolic activity, even at lower ethanol concentrations, so alcohol is cleared quicker from their bodies.

The good news is the overactive enzyme converts the alcohol almost instantly to acetaldehyde with all its unpleasant, hangover-causing side effects (5). This deters excess drinking, and thus alcoholism.

You may dread hangovers, but imagine a life without the negative reinforcement attached to drinking.  Appreciate the practicality of hangovers.

Many additional studies demonstrate that ADH1B, ALDH2 are protective against both alcohol dependence and excessive consumption (6).  The limitation with these studies is the populations are mostly European-ancestry.

People with mental illness also have a higher likelihood of using substances to cope with their illnesses.  Given the hereditary link to mental illness, this supports the influence of genetics on alcoholism, and falls under the category of dual diagnosis.

Adoption studies show that alcoholism in adoptees correlates more strongly with their biological parents than their adoptive parents (7-9).

 

Alcoholism and the Brain

 

Structural abnormalities in the brain are also linked to alcoholism.

Alcoholics and non-alcoholics in a family with a history of alcoholism show smaller amygdalae on average.  Specifically, “Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history” (10).  

In simplest terms, using a comparison of non-alcoholics in a family of alcoholics to non-alcoholics in a family of non-alcoholics, the latter group show smaller amygdalas.

 

Environmental/Social Causes of Alcoholism:

 

Environmental factors play important roles in the development of alcoholism.

An individual’s degree of economic development, age, and gender all contribute.

  • The poorer you are, the more at risk you are for developing alcoholism (less resources to cope/lower chance of seeking help)
  • Men suffer disproportionately more from alcohol-related disease
    • Thought to be from stronger dopamine release post consumption than in women= positive reinforcement) (11)
  • The earlier you start drinking, the higher risk you are for becoming an alcoholic

In addition, at the societal/geographic level, the availability of alcohol and the level/effectiveness of alcohol policies in the region play a part in determining alcohol-related harm (12).

 

Limitations:

The ALDH and ADH1 genes, while giving protection from alcoholism, are mostly seen in individuals of East Asian descent.  Thus, the genetic discussion above is limited in the spectrum of individuals it represents.

As for the neurological changes linked to alcoholism, plenty of confounding factors abound.  Many causes contribute to the size of the amygdala, for instance, not just the history of alcoholism in a family.  As the amydala is the “fight or flight” center of your brain, its size can increase or decrease based on cortisol (stress) levels in the individual.  It’s even shown to shrink post 8 weeks of mindfulness practice!

 

Conclusion:

Our best answer to the title question is that alcoholism arises from a complicated collision of genetic and environmental factors.  While you may be at risk or inherently protected based on your genome, there are plenty of ways to avoid environmental risk.

As genetic testing advances further and further, many will have the opportunity to test for their relative risk or protection from alcoholism and many other modern disease.

 

If you enjoyed this article, be sure to check out a popular article of ours detailing 21 Fun Facts About Alcohol !

 

References

  1. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4056340/#R20
  2. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4056340/ 
  3. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4056340/#R20
  4. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4056340/#R29
  5. //www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/adh1c
  6. //link.springer.com/article/10.1007/s11920-019-1008-1
  7. //www.ncbi.nlm.nih.gov/pubmed/8694681
  8. //www.ncbi.nlm.nih.gov/pubmed/7259422
  9. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4056340/#R13
  10. //www.nature.com/articles/npp2014187
  11. //www.sciencedaily.com/releases/2010/10/101018112308.htm
  12. //www.sciencedirect.com/science/article/pii/S0168827816304433#b0090
  13. //www.rightstep.com/alcoholism/binge-drinker-mean-im-alcoholic/ (Image Reference)

 

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