Key Genes to check for Alcoholism

Alcohol misuse is estimated to result in 3 million deaths worldwide each year (2016 numbers). Let that sink in…3 million people dying from overconsumption of alcohol.  According to the World Health Organization: “Mortality resulting from alcohol consumption is higher than that caused by diseases such as tuberculosis, HIV/AIDS and diabetes.”[ref]

This article explores the genetic connections to alcohol addiction and includes research-backed treatment options.

Alcoholism Runs in the Family…

You may have heard it said that ‘alcoholism runs in the family’… And some families do have more alcohol abuse problems than others.

For so many people, alcohol can wreak devastation on their lives — destroying their health, family relationships, longevity, and happiness.

Is alcoholism a disease?

Alcoholism is now often referred to as alcohol use disorder (AUD) or alcohol dependence. It is a diagnosable disease that is considered both physical and mental in nature.

While it is easy to dismiss alcohol dependence as being due to ‘not enough willpower’ or a ‘weakness’, the truth is, once established, alcohol dependence is due to physiological factors in addition to lifestyle.

One research study defines alcohol dependency as:

“Alcohol addiction is a chronic, relapsing brain disorder, which is characterized by a compulsion to seek alcohol, loss of control in limiting alcohol intake, and negative emotional state during withdrawal, in which genetic and environmental factors interact and appear to be equally important with respect to its development.”[ref]

Is alcoholism genetic or hereditary?

Sort of…the increased risk of alcoholism is a combination of genetic variants and drinking history, lifestyle, and (often) abuse.

Researchers estimate that about half of alcoholism is due to heredity. The other half is due to environmental factors (stressful life events, access to alcohol, friends and family drinking, etc.).

Essentially, the genetic variants are related to addiction (dopamine and serotonin systems) and alcohol metabolism. In the Genetic Variants section below, I’ll explain in more detail the genes related to alcoholism.

Physical addiction to alcohol: Stress hormone system

Why is alcohol addictive? It turns out to be a more complex question to get solid answers about than I thought it would be.

Research on addiction has focused on dopamine and the ‘reward system’ in the brain for a couple of decades. In a nutshell, dopamine releases in a way to reinforce or reward the brain for a behavior. It makes you feel good, so you seek to do it again.

Research does seem to back up the idea that dopamine is involved in the initial addiction process for alcohol use disorder. It gives you a buzz, which is pleasant and rewarding (until the next morning). You feel less stressed, perhaps happier for a while. But dopamine isn’t the whole picture.

Alcohol eventually changes the brain’s wiring.

Corticotrophin-releasing factor is part of the hypothalamus-pituitary-adrenal (HPA) axis, controlling the release of stress hormones in response to anxiety-inducing situations. In people with long-time alcohol use,  corticotrophin-releasing factor is altered in the amygdala. It changes the way the brain perceives and deals with stress — essentially turning the stress-response system on all the time.[ref]

The link between anxiety and alcohol use is self-evident, and many people experience stress relief when drinking in a socially anxious situation. Research shows that people with anxiety disorders progress from normal alcohol consumption to alcohol use disorder faster than the average.[ref]

Related article: Is Anxiety Genetic?

Animal studies clearly show the changes in the brain due to upregulated corticotrophin-releasing factor. Researchers find that chronic alcohol exposure increases corticotropin-releasing factor receptors, and the effects are long-lasting, even after the withdrawal of alcohol. Moreover, long-term alcohol exposure also modifies brain plasticity and physically changes how the brain copes with stress.[ref]

Additionally, alcohol use disorder may result from other mental illnesses such as depression, bipolar disorder, or schizophrenia.[ref][ref]

Members: Check your mood disorder risk factors on the Mood and Brain Topic Summary Report


Genetic variants linked to alcoholism:

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Addiction related genetic variants:

OPRM1 gene: encodes the mu-opioid receptor, linked to alcohol cravings and substance abuse

Check your genetic data for rs1799971 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: slightly stronger cravings for alcohol; more responsive to naltrexone for reducing drinking
  • G/G: increased cravings for alcohol[ref] more responsive to naltrexone for reducing drinking[ref]

Members: Your genotype for rs1799971 is .

SNCA gene: α-Synuclein protein

In addition to the genetic connection in a genome-wide association study, researchers have also found that alcoholics tend towards lower α-Synuclein levels. This protein interacts with dopamine, and it is also important in Parkinson’s development.[ref]

Check your genetic data for rs17015982 (23andMe v4):

  • G/G: increased risk of alcohol dependency[ref]
  • A/G: increased risk of alcohol dependency
  • A/A: typical

Members: Your genotype for rs17015982 is .

SLC6A4 gene: serotonin transporter, linked to addiction susceptibility

Check your genetic data for rs1042173 (23andMe v4, v5; AncestryDNA):

  • A/A: likely to drink more per day (in Caucasian alcoholics); increased craving for a drink[ref][ref]
  • A/C: somewhat increased cravings for drinking
  • C/C: typical

Members: Your genotype for rs1042173 is .

DRD2 gene: dopamine receptor, linked to addiction susceptibility

Check your genetic data for rs1076560 (23andMe v4, v5):

  • A/A: increased risk for alcohol dependency[ref]
  • A/C: increased risk for alcohol dependency
  • C/C: typical

Members: Your genotype for rs1076560 is .

DRD3 gene: dopamine receptor, linked to susceptibility to addiction

Check your genetic data for rs2134655 (23andMe v4; AncestryDNA):

  • T/T: increased risk of alcohol dependency[ref]
  • C/T: typical risk
  • C/C: typical

Members: Your genotype for rs2134655 is .

 

Metabolic or glucose-related genes

GCKR gene: glucose kinase regulator gene, important in regulating glucose in the liver

Check your genetic data for rs1260326 (23andMe v4, v5; AncestryDNA)

  • T/T: slightly increased risk of alcohol dependency[ref]
  • C/T: slightly increased risk of alcohol dependency
  • C/C: typical

Members: Your genotype for rs1260326 is .

KLB gene: β-Klotho protein, which links to FGB21

Check your genetic data for rs11940694 (23andMe v5; AncestryDNA):

  • A/A: greater alcohol consumption[ref]
  • A/G: typical alcohol consumption
  • G/G: typical

Members: Your genotype for rs11940694 is .

 

Genes related to alcohol metabolism

Some people feel bad after drinking alcohol due to alterations in how they metabolize alcohol into acetaldehyde. Unsurprisingly, it is linked to a decreased risk of alcoholism since it makes people not want to drink. Alternatively, not having any of the variants here is considered more of a risk factor for alcoholism – it depends on your perspective.

ADH1B  – Alcohol dehydrogenase gene:

Check your genetic data for rs1229984 (23 and Me v4, v5):

  • TT: faster metabolism of alcohol to acetaldehyde[ref], causes a build-up of acetaldehyde and feeling bad when drinking, reduced risk of alcohol dependency[ref]
  • CT: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, reduced risk of alcohol dependency
  • CC: typical risk

Members: Your genotype for rs1229984 is .

Check your genetic data for rs2066702 (23andMe v4 only; AncestryDNA):

  • GG: typical risk
  • AG: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, reduced risk of alcohol dependency[ref][ref]
  • AA: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde[ref]

Members: Your genotype for rs2066702 is .

ALDH2 – acetaldehyde gene:

Check your genetic data for rs671 (23andMe v4, v5; AncestryDNA):

  • AA: Alcohol flush reaction[ref], decreased risk of alcohol dependency
  • AG: Alcohol flush reaction, decreased risk of alcohol dependency
  • GG: typical acetaldehyde metabolism

Members: Your genotype for rs671 is .

ADH1C gene:

Check your genetic data for rs698 (AncestryDNA):

  • C/C: Increased risk of pancreatitis in people with alcohol dependency[ref]; slower conversion of alcohol to acetaldehyde[ref]
  • C/T: Increased risk of pancreatitis in people with alcohol dependency; slower conversion of alcohol to acetaldehyde
  • T/T: typical risk

Members: Your genotype for rs698 is .


Lifehacks:

If you carry the genetic variants related to alcohol use disorder and don’t drink a lot, the obvious ‘lifehack’ here is to continue avoiding drinking alcohol. Know that genetic susceptibility is real and apply that logically. Plus, alcohol really isn’t good for your liver, your brain, or your overall health.

Talking to your kids: If alcoholism runs in the family and you carry genetic variants that increase susceptibility, talk with your kids about it, starting before they become teenagers. Please give them the information about the heredity aspects of alcoholism to understand why they may be more at risk than their peers. Kids aren’t dumb, and giving them the facts about their risk is essential.

Getting the right help – Using genetics in alcohol use disorder.

If you have problems with drinking too much, please consider getting professional help.

  • If you have a personal doctor, that’s the place to start. Prescription medications can help reduce drinking, and your doctor will also know the local resources available.
  • In the US, there is a national treatment referral service hotline (confidential): 1-800-662-HELP (4357) or https://www.samhsa.gov/find-help/national-helpline.  The Alcohol.org website also has a rehab admissions navigator that helps find a place that accepts your insurance.
  • There are local alcohol abuse help services in every state, and community-based organizations in many places. You aren’t alone in this.
  • Cognitive Behavior Therapy, along with medications, is beneficial for many, especially for people with anxiety disorders.[ref]

Naltrexone is an opioid receptor antagonist that is FDA approved for alcohol dependence. Studies show that people with OPRM1 rs1799971 G-allele (in the genetics section above) respond better to naltrexone. G-allele carriers find that naltrexone blunts the cravings more.[ref]

Serotonin is also thought to be involved in alcohol addiction for some people. SSRIs seem to help reduce the number of drinks per day — but this is specific to variable number tandem repeat in the serotonin receptor gene and only for women.[ref]

Variable number tandem repeats are not included in 23andMe or AncestryDNA data, but some SNPs usually go along with the serotonin transporter repeats. So you can get a pretty good idea of whether you carry the long or short version. A couple of studies have found that two SNPs predict the long or short version of 5-HTTLPR fairly well – around 95+% of the time.[ref][ref][ref]  These are found in both v.4 and v.5 for 23andMe data.

5HTTLPR rs2129785
(23andMe v4, v5; AncestryDNA)
rs11867581
(23andMe v4, v5; AncestryDNA)
 Long  T  G
 Long  C  A
 Short  T  A

The above table can be kind of confusing – here is an example: If your rs2129785 genotype is T/T and your rs11867581 genotype is A/G, you would carry one copy of the 5-HTTLPR short and one copy of the long version.

For women with 5HTTLPR Long/Long – Ondansteron had better results

For women with Short/Short or Short/Long – Sertraline had better results.[ref]

Supplements and Natural Options:

Let me be upfront here: The research doesn’t show any prescription drug or natural supplement as a miracle cure for alcoholism for everyone. That said, supporting your overall health with nutrition and vitamins along with rehab or therapy may help make a recovery easier.

Dihydromyrecitin is an OTC supplement that counteracts alcohol withdrawal symptoms and reduces excessive alcohol consumption in animal studies.[ref] (I’m not finding any human clinical trials on it for alcohol, but it does help with NAFLD.)

A traditional supplement for alcoholism is Niacin. People who drink a lot tend to have nutrient deficiencies, including pellagra, which results from niacin deficiency.[ref] When it comes to supplementing with niacin, there are several forms available, including the older kind that makes you flush as well as non-flushing nicotinamide. Both seem to work for reversing niacin deficiency, so if you don’t like the flush, go with nicotinamide (also called niacinamide).

Excess alcohol does bad things to the intestinal barrier (leaky gut) and the gut microbiome. It allows more bacteria to slip into the bloodstream, adding to liver problems in alcoholism. Additionally, alcohol increases gut motility (hangover diarrhea, the beer shits…).

Studies show that you can reduce liver problems in alcohol use disorder by supporting the intestinal barrier function with zinc, niacin, prebiotics, and probiotics. The prebiotics and probiotics help replenish the good bacteria that make short-chain fatty acids, which are needed to regenerate the intestinal cells. MCT oil may also help with repairing the gut and liver problems from alcohol.[ref]

Animal studies show that berberine may also help with the alterations to the gut microbiome in alcohol use disorder. Berberine is a natural plant compound used in regulating blood glucose levels, and it also helps with bacterial overgrowth.[ref]

A B-complex supplement may help to improve vitamin deficiencies. Alcoholism modifies several B-vitamin levels in the body (in addition to niacin). Both folate levels and B12 can be impacted, as well as elevated homocysteine levels.[ref][ref]

Thiamine deficiency is a big problem in alcoholism as well. Estimates range from 30-80% for thiamine deficiency in people with alcohol use disorder.[ref]

Whatever you choose to do, research shows that most interventions will help to reduce the number of drinks per day. Seek help, try multiple interventions, and take care of your overall health. [ref][ref]


Extras for Members:

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Related Articles and Genes:

L-theanine for anxiety: genetics and nature’s chill pill
L-theanine is known for reducing anxiety and promoting sleep. Discover the many benefits of l-theanine and how supplementation might work for you.

Alcohol Genes: Alcohol Metabolism Rate
Wondering why you don’t react the same way to alcohol as your friends do? Some people metabolize alcohol faster leaving a build-up of acetaldehyde. Learn more about why this can be a health problem for some. (Member’s article)

Metabolic Health Topic Summary Report
Metabolic health is important for your overall well-being. Learn how to optimize your health using your genes and our topic summary report.

Berberine: Research studies, Absorption, and Genetics
Berberine is a supplement that I’ve written about as a ‘Lifehack’ in a number of different articles. It is a natural compound with some amazing research on it in animal and cell studies, and it seems to be almost unbelievable. The drawback seems to be poor absorption in the intestines decreasing its effectiveness.

 

 

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Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.