Susceptibility Does Not Mean Inevitability
When scientists look for “addiction genes,” what they are really looking for are biological differences that may make someone more or less vulnerable to addiction. It may be harder for people with certain genes to quit once they start. Or they may experience more severe withdrawal symptoms if they try to quit.
Factors that make it harder to become addicted also may be genetic. For example, someone may feel sick from a drug that makes other people feel good. But someone’s genetic makeup will never doom them to inevitably become an addict. Remember, environment makes up a large part of addiction risk.
Many Genes Influence Addiction
Scientists will never find just one single addiction gene. Like most other diseases, addiction vulnerability is a very complex trait. Many factors determine the likelihood that someone will become an addict, including both inherited and environmental factors.
Because addiction is a complex disease, finding addiction genes can be a tricky process. Multiple genes and environmental factors can add up to make an individual susceptible, or they may cancel each other out. Not every addict will carry the same gene, and not everyone who carries an addiction gene will exhibit the trait.
However, multiple lines of research show that addiction is influenced by genes.
When Addiction Runs in the Family
Because addiction has an inherited component, it often runs in families. That is, it can be passed down from parent to child by way of genes. The pedigrees, or family trees, to the left show affected individuals in red and unaffected in white.
Researchers often study large families to learn which genes may be making them susceptible to addiction. They begin by comparing DNA sequences of family members who are affected by addiction with those who are not, and they look for pieces of DNA that are shared among affected individuals and less common in the unaffected.
Because people have complex and varied lives, researchers often look to animal models to learn more about the genetics of addiction.
Discovering Addiction Genes
Many genes with roles in addiction were identified with the help of animal models, especially mice. Because the reward pathway—and many of the genes that underlie it—functions in much the same way in mice as it does in people, mice are leading the way in identifying addiction genes.
When researchers discover a gene that plays a role in addiction in a model organism, such as mouse or fruit fly, they can then identify the counterpart gene in humans by looking for similar DNA sequences.
To the right, you will find a sampling of some of the genes suspected to play a role in addiction, many of which were identified first in animals.
- The A1 allele of the dopamine receptor gene DRD2 is more common in people addicted to alcohol or cocaine.
- Mice with increased expression of the Mpdz gene experience less severe withdrawal symptoms from sedative-hypnotic drugs such as barbiturates.
- Mice without the cannabinoid receptor gene Cnr1 are less responsive to morphine.
- Mice lacking the serotonin receptor gene Htr1b are more attracted to cocaine and alcohol.
- Mice bred to lack the β2 subunit of nicotinic cholinergic receptors have a reduced reward response to cocaine.
- Mice with low levels of neuropeptide Y drink more alcohol, whereas those with higher levels tend to abstain.
- Fruit flies mutated to be unable to synthesize tyramine remain sedate even after repeated doses of cocaine.
- Mice mutated with a defective Per2 gene drink three times more alcohol than normal.
- Non-smokers are more likely than smokers to carry a protective allele of the CYP2A6 gene, which causes them to feel nausea and dizziness from smoking.
- Alcoholism is rare in people with two copies of the ALDH*2 gene variation.
- Mice lacking the Creb gene are less likely to develop morphine dependence.
From Genes to Treatment
One goal of genetic research is to help develop improved treatments. Each new addiction gene identified becomes a potential “drug target.” That is, researchers can focus on one gene product and develop a drug that modifies its activity. In so doing, signals or pathways in the brain may be modified or stabilized to restore proper brain function.
Understanding the role of genetic variation in addiction genes can also help inform treatments. The effectiveness of medications vary from person to person, depending on their genetic make-up. In the future, genetic tests could be used to determine which medications are likely to be most effective based on an individual’s genetic profile. Learn more in Precision Medicine.