SNPwatch: Evidence for Gene-Environment Interaction in Alcoholism

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Addiction to alcohol is associated with the brain’s reward system, which reinforces behaviors that feel good — like drinking — by releasing neurotransmitters such as dopamine and endorphins. With prolonged alcohol consumption, a person’s brain can gradually adapt to the point that excessive amounts of drinking are required in order to produce the same pleasure response, and alcoholism results.

That means genetic factors that influence the biochemistry of the reward pathway, as well as environmental factors that encourage alcohol consumption (such as peer pressure and stress) can increase a person’s alcoholism risk.

Researchers have long suspected that a combination of genetic and environmental causes can act together, increasing alcoholism risk more than either acting alone. But so far little evidence has been found for such an effect.

A new paper to be published in the December issue of Alcoholism: Clinical and Experimental Research has found evidence for a synergistic effect between a genetic variation and level of education in a study of 700 Mexican-Americans. The prevalence of alcoholism among Mexican-Americans is relatively high; Mexican-American men report past heavy drinking at three times the rate of men belonging to other ethnicities.

The researchers, Yanlei Du and Yu-Jui Yvonne Wan of the University of Kansas Medical Center, measured three genetic variants associated with the function of chemicals involved in the brain’s reward system. They also looked at marital status and education level in the study participants.

The study found that of the three genetic variants, two were associated with severe alcoholism (defined by consuming more than 35 drinks per day).

o Having two copies of the A version at the SNP rs1799971, which is located on the opioid receptor gene OPRM1, increased the odds of severe alcoholism 2.16 times.
o Having two copies of a variant in the DRD2 gene, which affects the structure of a receptor for the neurotransmitter dopamine, increased the risk of severe alcoholism 1.85 times.

(23andMe customers can see their data for rs1799971 and rs1799732, which is diagnostic of the DRD2 variant, using the Browse Raw Data feature. For rs1799732, a result of II indicates the riskier variant. SNP rs1799971 has previously been associated with the need for morphine as pain relief after surgery as well as sensitivity to social rejection.)

Of the two environmental factors, only education level had an effect. Those with less than 12 years of education had 1.97 times the odds of severe alcoholism. (Having less than 12 years of education also increased a person’s odds of less-severe alcoholism by about the same amount.)

But when the researchers considered combinations of the three associations, they found that having two A copies of the OPRM1 SNP rs1799971, combined with less than 12 years of education, increased a person’s odds of severe alcoholism 3.3 times.

The researchers suggest that a low education level may magnify the effects of the OPRM1 variant, or that higher education may mask its effects by improving brain function.

However, other factors might be responsible for the effect. For example, it is possible that those who attain an education past high school have other characteristics that make them less likely to become addicted to a substance.

There is no way yet to measure an individual’s vulnerability to alcohol addiction, and the complex interaction between genetics, education and other environmental factors must be further studied to clarify the causes of alcoholism in this and other ethnicities.


  • darkeyes

    I am interested in this, because my father is a “functional” alcoholic, and drank heavily in the past. I am AA for the rs799971 SNP, which concerned me, and so I researched this to determine why the alcoholics in this small study drank more. Although I do not drink, I have an 11 year old son about to enter the teen years. I was puzzled about this: the “A” SNP is relatively common, the people with the G SNP have more of a chance to be addicted to heroin in another small study, and then I read this study:

    http://www.ncbi.nlm.nih.gov/pubmed/17207095?dopt=Abstract

    which indicates the people with the “G” SNP tend to “crave alcohol more” and respond to naltrexone therapy better than those with A (in yet another study). One of my “traits” is that I would not likely respond as well to naltrexone (a dopamine antagonist) therapy if I were treated for alcoholism or opiate addiction.

    My conclusion is that with AA for this SNP, my dopamine DR 2 receptors do not bind dopamine as tightly, so that I would not reach such euphoria as easily when drinking alcohol, or using heroin (which I have never tried). I would have to drink more alcohol to achieve the same “buzz”, and thus would tend to drink more daily if I became addicted to the effects of alcohol (which does raise dopamine levels – hence the addictive nature of this substance). I feel remarkably well when I exercise, due to endogenous endorphins, but I exercise quite a lot, and I guess that is why.

    The same likely applies to the SNP rs1799732, of which I am “II”. It also affects the structure of the dopamine DR 2 receptor, and I believe in a similar way to the 1799971 SNP, so that one would have to drink more (or exercise more) to get the same positive reinforcement effect. I could not find much info on this one.

    Finally, I have one “defective” gene coding for the aldehyde dehydrogenase enzyme, that makes me flush and increases my risk of esophageal cancer if I drink – the more the worse chance. I’ve had this unpleasant flush/nausea experience in the past when i did try alcohol. I therefore will continue to avoid alcohol. I will likely have my son’s genome checked some day.

    By the way, I am heterozygous for rs 1800497, the SNP which is most studied regarding addiction. This gene works in a different way. People with one or two of the A1 allele (and I therefore have one), can have more addiction problems for different substances, but many with two A1 alleles do not have addictions. It is not definitive for these diseases, like many other gene-disease relationships.

    One thing about this is that the study cited in this article, and others, are small studies, and have not proven that any one or more genes is highly responsible for addiction. Environment, including educational status, and your life experience (seeing the way dad acted, for example), can be very protective against addictions.

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