The Role of Genetics

 

Why do some people become addicted while others do not? Substance use disorders (SUDs) often run in families. Researchers have studied families with high rates of addiction and found that about half of a person’s risk of developing a SUD depends on his or her genetic makeup. Pinning down the biological basis for this risk is an important avenue of research that will help scientists develop better, more personalized prevention and treatment strategies.

Many Genes Influence Substance Use Disorders

Genes are the basic units of our DNA that direct the development and functioning of every cell in our bodies. Research has shown that, on average, the DNA sequences of any two people are 99.9 percent the same. But that 0.1 percent variation is important. These differences contribute to visible differences between people, such as height and hair color, as well as invisible traits, such as increased risk for certain health conditions like heart attack, stroke, diabetes, and addiction.

Some diseases, such as sickle cell anemia or cystic fibrosis, are caused by an error or “mutation” in a single gene. However, most diseases, including SUDs, are much more complex. Variations in many different genes contribute to a person’s overall level of risk or protection from a SUD. In addition, environmental factors like quality of sleep, diet, or stress, can directly influence how genes act.

Genes that Influence Substance Use Disorder

So far, most of the genes that researchers have found to influence the risk for a SUD fall into a few categories:

  • Genes that influence how we respond to a substance - For example, some people have a gene variation that makes them feel dizzy and sick when they smoke cigarettes. People with this variation are less likely to become smokers.

  • Genes that influence how we metabolize a drug - For example, some people carry a gene that makes them metabolize opioids faster. Studies suggest that they may be more susceptible to opioid use disorder.

  • Genes that influence how we respond to treatment - For example, one study found that people with a gene that causes them to metabolize nicotine slowly do better when treated with the nicotine patch, while those who metabolize nicotine at a normal rate do better with the medication varenicline (Chantix®).

  • Genes that influence personality traits - For example, people who are more impulsive or sensitive to rewards are more likely to try substances and to develop SUDs.

Substance Use Disorders are not Inevitable

People who have genetic risk factors for substance use disorders are more likely to try drugs and alcohol and to develop SUDs but these outcomes are not guaranteed. Prevention programs targeting high-risk youth can reduce or delay the initiation of substance use and people with high genetic risk can be successfully treated if they do develop a SUD.

If you or someone you love has a family history of addiction, there are many strategies that can help reduce one’s risk, including:

  • Delaying initiation of substance use: The adolescent brain does not finish developing until the early to mid-20s, which is why teens are much more susceptible to developing SUDs than adults. Delaying the initiation of substance use until the brain has fully developed substantially reduces the risk for a future SUD.

  • Training in skills that address environmental risk factors, such as

    • Managing and coping with stress

    • Communicating needs and feelings

    • Refusing substances that are offered

  • Supporting protective factors, such as

    • Increasing parental involvement

    • Fostering positive passions (e.g. sports, music, science, etc.)

    • Mentoring

Knowing that you or your loved one is at increased risk for a SUD can help you take steps to reduce these risks and stop the cycle of addiction that is common in so many families.

How Understanding Genetics Can Improve Treatment and Recovery

Understanding how our genes influence SUDs can pave the way for precision medicine - where medical care is tailored to a person’s individual genetic risks. Precision medicine for a SUD could include targeting prevention strategies to people who are at high genetic risk for the disorder; regular SUD screening for those at high-risk; and tailoring treatment plans based on a patient’s specific genetic makeup - including identifying medications and dosages that work best for patients with specific gene variants.

Understanding a patient’s genetic risk for opioid use disorder can also help doctors minimize the risk for opioid misuse and addiction when treating a patient for pain. Such information could help doctors to be more cautious when prescribing an opioid for pain relief prescription, adjust the dose or duration of treatment, and screen more often for signs of misuse among high-risk patients who have been prescribed opioids.


Learn more:

Genetics and Epigenetics of Addiction (NIDA)

 

 

Q&A — “The Role of Genetics in SUD,” with Dr. Ruben Baler, Ph.D., Health Scientist Administrator, NIDA.

  • Q. What does it mean that addiction runs in families?

    A. We are all familiar with the concept of genetics influencing personal characteristics. Sometimes, they are the result of a single gene, like your blood type. In other cases, like various cancers or Down syndrome, we know there are many genes at work. The risk of drug misuse and addiction is similarly influenced by the combined actions of many genes.

    Researchers have identified hundreds of genes that influence risk for addiction; these genes impact a wide range of characteristics, from an impulsive or risk-taking temperament to how a person’s body metabolizes a drug, and even to how someone feels when they take a drug. These kinds of traits are the result of complex biochemical processes involving whole constellations of genes acting in concert.


    In short, the risk for drug use and addiction is affected by the sum total of many different characteristics of a person, and each of those characteristics is influenced by many different genes. So there is no single “addiction gene.”

    But it’s very important to realize that many of the genetic constellations that can make a person more likely to engage in risky behaviors, like using drugs, can, under a different set of circumstances, nudge them toward taking the kinds of risks that might make them a great public speaker or salesman, a brilliant scientist, a competitive runner, a creative entrepreneur, or a deep-sea explorer.  

    Having some understanding of the genetic risk in a family can be an empowering piece of information. Properly used, it can really give parents a vital “heads up” and assist in their efforts to shape the developmental trajectory of their children in a more personalized and protective fashion.
  • Q. How much of the overall risk of addiction comes from our genes?
    A. The short answer is: about half.

    One of the best ways to estimate genetic contribution for any characteristic is by studying many pairs of twins. We ask the following question: If one twin has a particular trait, what are the chances that the other will have it too? The results, calculated over many pairs of twins, both identical and non-identical, give us what’s called the “concordance” value, a measure of how strongly or weakly the characteristic is shared between those genetically related individuals, and thus, the strength of the genetic contribution.

    So, for example, 100 percent of identical twins have the same eye color, but only 40 percent of non-identical twins do, indicating that eye color is 100 percent genetic. On the other end of the spectrum, we can look at traits like the risk of coming down with measles. The odds for these kinds of traits are exactly the same between siblings, regardless of whether they share all (as identical twins) or about half (as in non-identical twins) of their genes. This indicates that these traits are zero percent genetic (and thus 100 percent environmental).

    The concordance for addiction is higher for identical than for non-identical twins and it falls somewhere in the middle of the range, at around 40 to 60 percent, indicating that about half of the risk is genetic and the other half is environmental.

    However, and this is very important, this does not mean that environmental and genetic factors independently influence the risk of drug use and addiction. It turns out that environmental factors, like sleep quality, diet, or stress, can directly influence what our genes do. For example, a nurturing environment during early childhood can modify how genes involved in an individual’s stress response are expressed, in a way that better prepares a person to handle stressful situations later in life. We are learning more and more about how different personality traits, like a penchant for seeking new experiences or liking to take risks are linked to aspects of a child’s early environment, during the period when their brain is most actively being “programmed” by their experiences.
  • Q. Is it possible to identify if a person has a risky gene? And can we “fix” it?
    A. Not really. There is no single “addiction gene,” but hundreds of interacting genes contributing to addiction risk. We don’t yet know all of the genes that are involved, and there is no way to tweak just the ones that are relevant. But even if there was some way to “fix” a person’s genes, we would not want to do it. Again, the same genetic factors that put us at risk in one set of circumstances can promote success in a different context. The smart money is in understanding and modifying that context – or environment - to channel that person’s inborn tendencies in positive directions.
  • Q. If addiction runs in my family, does it mean I am destined to be addicted too?
    A. No. Genes would only spell doom if we had a small number of genes that were either always good or always bad, no matter what. But that’s not how it works.

    The influence of individual genes on behavior is small in size and highly dependent on environmental factors.

    This is why knowledge about family history can be so empowering. If we know we are at increased risk we can take steps to boost our protective factors. Scientists have devised trainings and educational programs that make us more resilient against a wide range of environmental threats. When these are deployed during a child’s formative years, they can be highly protective in a personalized sort of way. Take the same example of a strong personal or familial tendency for risk-taking. Parents who recognize this early on can structure the life of a child around safe and age-appropriate activities that not only channel that tendency away from self-destructive behaviors but actually nurture more positive and healthy expressions of it—like martial arts, scuba diving, or engineering competitions. For a kid with a tendency to take risks, there are healthy ways to express it that harness the power of intrinsic motivation while promoting wellbeing and resilience.