Genetics and Addiction

Genetics and Addiction Overview

Addiction is highly complex that can be associated with environmental and genetic factors. Often, whether behavioral- or substance-driven, addictions are frequently chronic and have a common course which includes cycles of abstinence and relapse. Genetic researchers are making strides in trying to clarify the origins of addiction and whether or not a person’s genes could lead to a predisposition to addiction, especially substance misuse and dependence. Researchers hope to be able to identify new therapeutic methods in addition to improved treatment response and overall prevention.

Substance and Process Addictions

Characterized by compulsive, uncontrolled use of an activity or substance, addiction will lead to maladaptive, destructive outcomes if not treated. Craving, intoxication, withdrawal, and negative effects are the four primary characteristics of addiction. Both substance and process addictions have been found to induce adaptive changes in the reward regions of the brain which leads to a tolerance and habit along with substance- and action-seeking, compulsive-like behavior. Neuroadaptive changes are considered to be a key element in relapse. Genetic researches attempt to identify to what extent addiction is influenced by inherited genes, and how much environmental factors might have to do with the development of a dependency.

Genes and Addiction

It is widely accepted, based upon extensive studies, that there is no single addiction gene. Rather, like other diseases, vulnerability to addiction is complex and determined by several factors including genetics and environment. That said, there are genes which can add up and render a person susceptible to addiction. Likewise, various genes can also cancel one another out. Furthermore, not all addicts will carry the same gene, and every person who does have addiction gene will not exhibit or develop the trait. This has made genetic research difficult to navigate, but progress made has shown that addiction can be influenced by genes.

Family History of Substance Dependence

When participants in genetic studies have been questioned about why they chose to avoid substances, or on the other hand, chose to use substances, many had similar reasoning. Those who avoided the destruction of addiction often attributed their success to a loving, supportive family member, friend, or teacher who guided them through troubling times. Others had set, and stuck to, specific goals such as going to school or maintaining a relationship. Likewise, participants who ended up with an addiction were found to attribute their path to having an addictive personality, bad friends, or parents who also had an addiction.

It would be naive to think that a family member’s addiction would not have an impact on a person’s own behavior and patterns. However, contrary to what is read on headlines and spread through word of mouth, there is no single gene that causes alcoholism or drug dependency. This is not to say that genetic factors can’t be contributors. A number of research groups have studied twins to identify how much addiction risk, particularly alcoholism, can be linked to genes compared to environment. One study showed 48-58 percent of the variation in susceptibility to alcohol dependence was attributed to additive genetic factors. The remainder could be attributed to environmental influences that were not necessarily shared with other family members.¹

Addiction to illegal drugs, such as cocaine, has only more recently been studied in twin samples. Thus far, the results suggest that genetic influence contributes to between 45 and 79 percent of the dependency with the remainder being environmental. ² Other studies have shown very similar outcomes including the 2013 twin study which suggested that genetics and nonshared environments did influence alcoholism, binge eating, and compensatory behaviors. Genetic associations were estimated at being 38-53 percent responsible.³

In addition to studying twins, researchers have tried to study large families to better learn about which genes could make a person more susceptible to an addiction. In order to do this, DNA sequences of addicted family members are compared to those who do not have an addiction. The researchers then look for DNA markers that are shared amongst the addicted members and not as prevalent in the members who are unaffected. ⁴ Even with this DNA comparison, there are still complex factors to consider which is why researchers also look to animals to gain an understanding of this issue. In all of their findings, indications match those found in the twin studies which suggest there are genetics that could make a person more vulnerable to developing a drug or alcohol dependency.

More than Genetics in Addiction

Although there is truth in that people with a family history of dependency tend to also drink or use more, this is far from a cause and effect chain reaction. Often, it is easier for a person to cope with a problem like addiction by justifying or blaming it on one source. Unfortunately, life is far more complicated to simplify addiction in such a manner.

The human mind is an intricate system and ignoble motives do not always lead to ignoble behaviors. In fact some counteract others. The likelihood of addiction is influenced by more factors than can be counted on two hands and include genetics, culture, peer groups, parenting, expectancies of what the substance will do, the body’s response to the substance, and by chance events of the wiring of the brain during utero.

In addition to environmental factors, there are behaviors that could pose a problem if left unaddressed. For instance, someone experiencing depression, ADHD, anger, compulsive disorders, or other disorders may be at more risk for developing an addiction. Whether or not the aforementioned are genetically inherited or adapted over the course of a person’s life may be better understood when individually evaluated by a medical professional.

Although addiction can run in a family, or a person may experience trials and tribulations that make him or her prone to dependency, does not mean they have to fall victim to the trap of addiction. In fact, it may be safe to say that everyone has the potential to become addicted to something. It is perhaps the coping skills that a person has with such obstacles that play a major role in how susceptible one really is to dependency. When, and if, addiction does occur, it is important for the addict to remember that while they may not have control of their genes or their childhood, they do have control over how they choose to move positively forward.

Research on Genetic Susceptibility to Addiction

The Collaborative Study on the Genetics of Alcoholism (COGA) is a very large family study which has been ongoing since the 80s.⁵ It is designed to help researchers identify genes that affect a person by making them at risk for alcoholism and alcohol related behaviors. The study is taking place in nine different states and is funded by the National Institute on Alcohol Abuse and Alcoholism. An updated summary can be read in full in COGA’s recent release; however, what the ongoing study has been able to suggest so far includes:⁶

• Several regions DNA chromosomes (chromosome region 1&7, and partially region 2) appear to contain genes that affect the risk for alcoholism
• An analysis of a protective region on chromosome 4, in the general vicinity of the alcohol dehydrogenase (ADH) genes, suggest that a of a variant or variants of this gene might reduce the risk of alcoholism.
• Many people studied under COGA exhibited diagnostic criteria for major depressive disorder. Depression and alcoholism has been linked to chromosome 7 and 2. This suggests a gene within this chromosomal region could increase the risk for both of these disorders.

The Texas Biomedical Research Institute recently studied a group of 1,064 people in the US who had a family history of alcohol.⁷ Their brain waves were scanned repeatedly to find genes that were directly associated with these waves. The genomewide scan revealed a strong link with a variation of the serotonin receptor gene named HTR7. Their findings suggest that there is a strong correlation between serotonin levels and drinking patterns.

Born an Addict

A sizable minority of addicts are second, third, or even fourth generation alcoholics which has led many to question whether or not one can be born and addict. Although we have already discussed the genetic and environmental factors of addiction, this question is worth taking a moment to address. The term ‘born an addict’ does not mean that a baby is born under the influence -– although this can happen when a baby is born from an active, addictive mother. Born addicts on the other hand are said to be predisposed to addiction both genetically and environmentally. As soon as he or she is introduced to alcohol, or a drug, they are motivated to drink or use compulsively.

Neuroscientists argue this in lieu of two specific factors:

• That genetic predisposition is not destiny, and
• that genes constantly interact with the environment.

So what is going on externally can essentially turn on or turn off genetic activity — could either reinforce or counteract any genetic predisposition. For instance, a parent who is very supportive of their child could reduce the risk of addiction even when a child has a high risk of dependency such as coming from a family with a long history of addiction. Conversely, a child who has experienced severe trauma could be at more risk for addiction and depression even if there is no family history of dependency.

The second factor of the born addict argument is that, when a person is able to recognize that he or she meets the characteristics of a born addict, and immediately drinks or uses from the first time, the explanation of why they are doing so is clear. Thus, the only practical course of action is treatment. Whereas a person who develops a progressive addiction — through use, abuse, tolerance, and addiction — will not be able to take this route.

Getting a born addict into treatment may be easier said than done, especially because they are often very young and exhibit a rather robust form of denial. On the other hand, the born addict might realize the seriousness of the repercussions and be willing to get treatment more quickly than a person who develops an addiction over time. While neuroscientists believe there is a spectrum of risk in association with genetics and environmental factors, there has been no research to demonstrate that a person can actually, and quite literally, be born an addict.

Further Genetic Studies Related to Addictions and Behaviors

Apart from researchers looking for direct genetic linkage to dependency, other studies have been able to successfully identify SNPs, genes, alleles, and polymorphisms that can are responsible for altering behaviors or make a person more or less susceptible to addiction.

• rs53576: A SNP with a silent G to A change in the oxytocin receptor gene exhibits. This SNP is responsible for social behavior and personality.⁸ Research has shown that people who have a G allele are more empathetic, employ more sensitive parenting techniques, and feel less lonely. Variations in the oxytocin receptor gene typically relate to empathy and reactions to stress; in general, those who have the G genotype are able to discern the emotional state of another person than those who have the A genotype.
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• rs1800497: A SNP known as the Taq1A polymorphism of the dopamine D2 receptor gene. This gene has been associated with a reduction in dopamine binding sites within the brain as well as a reduced response to errors, and an increase in addictive behavior.⁹ It is speculated to have an influence in alcohol dependence, smoking addiction, and some neuropsychiatric disorders.
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• rs1799971(G) – As an allele of the mu opioid receptor gene, studies suggest it causes the amino acid asparagine to be replaced by aspartic acid.¹⁰ Researchers believe this change can cause people to have stronger cravings for alcohol; therefore, may be prone to an addiction. Subsequent study results are mixed leading to some disagreements in this finding. A notable study furthering the interest of this gene involved alcoholics who were treated with naltrexone and no behavioral intervention. Over 200 of these patients had an increase in abstinent days and a decrease in heavy drinking days; whereas, people with the rs1799971(A) genotype showed no difference in medication. It is also thought this SNP may influence the response to opioids including heroin and morphine.

Alcoholism and SNP Genes

A number of SNPs have been linked to alcoholism including the tendency to drink more or to treat the dependency itself.¹¹ These include:

• GABRA2: Noted for polymorphisms and alcohol risk dependence
• rs27072 and rs27048: Associated with an increase in the severity of withdrawal symptoms including seizures
• rs1076565: Potentially important in the development of alcohol dependency
• rs1042173: May predict heavier drinking patterns amongst caucasian alcoholics

Drug Abuse and SNP Research

SNP research on drug abuse and dependency is limited; however, there are ongoing studies that are looking promising. Thus far the following SNPs have been identified:

• rs135745: This SNP has been associated with the sensitivity to d-amphetamines acute effects. Sensitivity to psychoactive drugs is thought to cause an heightened risk of drug abuse.¹² Separate studies in a Japanese population were unable to confirm this.
• rs324420: A SNP in the fatty acid found in the FAAH gene rs324420^. It is thought to increase the risk of substance abuse, including drugs like marijuana.

Addiction Genes

SNP genes that may be linked to addiction are broad and require more research. Over the last decade or more, the following SNPs, but not exhaustively listed, are believed to be intertwined with addiction:

• rs1534891: An SNP thought to be part of an SNP interaction that is associated with bipolar disorder, heroin addiction, and prostate cancer.¹³
• rs686: Implicated as part of the dopamine DRD1 receptor gene that has been linked to autism and other related disorders.¹⁴ It is also thought to be linked to tobacco smoking, alcohol dependence, impulsive behavior, aggression, ADHD, and schizophrenia.
• rs1076560: Part of the D2 dopamine receptor gene, this SNP exhibits a heightened risk of alcoholism, opiate addiction, and even dosage requirements for methadone substitution.¹⁵

See also the SNPedia Addiction category for SNPs related to addiction.

Conclusion

Although it can be concluded that there is no actual addiction gene, nor can anyone be born an addict, there are genetic markers that can indicate a person predisposed to process- and/or substance-dependency. As research progresses, professionals in the addiction community hope to discover new treatment methods that coincide with the study outcomes. In the future, gene therapy may indeed become available to help counteract predispositions toward addiction.

Sources:

1. Genetic and Environmental Contributions to Alcohol Abuse and Dependence in a Population-Based Sample of Male Twins ↩
2. The Genetics of Alcohol and Other Drug Dependence ↩
3. A Twin Study of Alcohol Dependence, Binge Eating, and Compensatory Behaviors ↩
4. Genetics and Addiction ↩
5. The Collaborative Study on the Genetics of Alcoholism: Overview (pdf) ↩
6. The Collaborative Study on the Genetics of Alcoholism: An Update ↩
7. Brainwave study reveal link to serotonin gene and alcoholism ↩
8. rs53576-SNP ↩
9. rs1800497-SNP ↩
10. rs1799971-SNP ↩
11. Alcoholism genes in SNPedia ↩
12. rs135745-SNP ↩
13. rs1534891-SNP ↩
14. rs6861-SNP ↩
15. rs1076560-SNP ↩