The Effect of Genes on Addiction

Genes and their effect on Drug addictions

Why do some people become addicted while others don't? Previous studies including studies of families that consist of identical twins, fraternal twins, and siblings, suggest that as much as half of a person's risk of becoming addicted to nicotine, alcohol, or other drugs depends on their genetic makeup.

The field of Genetics is the study of genes. Genes are functional units of DNA that make up the human genome. They provide the necessary information that is needed to direct the body's basic cellular activities. An interesting fact is found through research on the human genome indicates that the average DNA sequence of any two people is 99.9 percent similar. This does not mean that the other 0.1 percent variation is profoundly important. This small amount of base sequences account for three million differences in the nearly three billion base pairs of DNA sequence! These differences contribute to visible variations, like height, and invisible traits, such as increased risk for or protection from certain diseases such as heart attack and addiction.

Epigenetics is the study of functional, and sometimes inherited, changes in the regulation of gene activity and expression that are not dependent on gene sequence. Environmental exposures can actually change the structure of DNA at the cellular level. Although each cell type in the human body effectively contains the same genetic information, epigenetic regulatory systems enable the development of different effects on the contained genetic information in response to specific environmental factors. These epigenetic marks can affect health and even the expression of the traits passed to children. When a person uses cocaine, it can mark the DNA, increasing the production of proteins common in addiction. Increased levels of these altered proteins correspond with drug-seeking behaviors.

Histones provide an organizational structure for genes. Genes coil around histones, tightening or loosening to control gene expression. Drug exposure can affect specific histones, modifying gene expression in localized brain regions. Research has shown that manipulation of histone-modifying enzymes and binding proteins may have promise in treating substance use disorders.

A Gene Linked to Cannabis Use Disorder

It is estimated that 30% of marijuana users have a cannabis use disorder, representing problematic and a possibly severe addiction. The risk for habitual uses of cannabis, has a strong genetic component. However research hasn’t clearly identified the genetic architecture. Scientists recently performed a genome-wide association study to try to identify genes that might put people at risk for problematic cannabis use. They studied 2,387 cases and 48,985 controls, and were able to replicate their findings in a larger group. They identified a genetic locus on chromosome 8 that controls the levels of the gene CHRNA2 expressed in the brain. Low levels of expression of the gene CHRNA2 in the cerebellum are found to be associated with cannabis use disorder, including diagnosis at an earlier age. In addition, genetic factors associated with educational attainment were found to be protective against the disorder. The findings suggest that under expression of CHRNA2 in the cerebellum and probably other brain regions is involved in cannabis use disorders, and provides a potential target for future prevention strategies, therapies and medications.

Advances in DNA analysis are helping researchers untangle complex genetic interactions more efficiency and accuracy in determining addiction predisposition. Researchers are now able to examine a person's entire genome all at once. These technologies are used in genome-wide association studies. When looking at the exome sequencing scientists are able to look at just the protein-coding genes and are able to identify subtle variations in DNA sequence called single-nucleotide polymorphisms. Single-nucleotide polymorphisms are differences in just a single letter of the genetic code from one person to another. If a single-nucleotide polymorphism appears more often in an individual with an addiction than those without, it is thought to either directly affect susceptibility to that disease or be a marker for another variation that does.

These methods allow scientists to gather more evidence from affected families or use animal models and biochemical experiments to verify and understand the link between a gene and the risk of addiction. These findings would then be the basis for developing new treatment and intervention approaches and will allow us to understand the effects on drugs and addiction!

Figure 1: Provides visual context of the information discussed in this blog, with data and supporting images.

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