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.