Have you ever wondered why some people can smoke cigarettes for a year before just quitting, while others develop a lifelong addiction? Why can’t some people stop consuming alcohol, while others can do without? A person’s hereditary tendency to use drugs is a factor.
Researchers at the UNC School of Medicine led by Hyejung Won, PhD, are beginning to understand these underlying genetic variations. The more they discover, the more likely it is that scientists can develop therapies to help the millions of people battling addiction.
Won, an assistant professor of genetics and a researcher at the UNC Neuroscience Center, and his team discovered genes linked to drinking alcohol and smoking cigarettes.
The scientists found that certain types of neurons — brain cells that cause other cells to send chemical messages through the brain — have an excess of these genes.
The researchers, whose findings were published in the journal Molecular
Psychiatry, also found that the genes linked to smoking were:
connected with the feeling of pain and how the body reacts to food, moreover
on the use of other drugs such as cocaine.
Stress, learning and the use of other drugs such as morphine were also linked to other genes linked to alcohol use.
The researchers also conducted assessments of a publicly available pharmacology database to find possible new treatments for substance
abuse because there are currently few alternatives to substance use treatment
disorder.
According to Nancy Sey, a graduate student in the Won lab and the newspaper’s first
author, “We found that antipsychotics and other mood stabilizers may
able to provide therapeutic treatment to those who struggle with substances
abuse”.
And we are confident that our research will serve as a solid platform for studies
aimed at developing more effective drug addiction treatments.
Numerous common diseases and problems, including lung cancer, liver
illness and mental illness are related to long-term substance use
and substance use disorders.
However, there are not many therapy choices, mainly because we do not fully understand the underlying molecular mechanisms.
According to Won, “twin studies have shown that, in addition to contextual
factors such as family dynamics or personal trauma, genetics may also play a role in
why certain people use and abuse drugs.”
Won said that by comparing individuals who exhibit a trait to those who:
no, researchers can use GWAS to locate specific regions in the genome
that contribute to that characteristic. However, genome-wide research cannot
a lot of insight into how the genes in those areas influence a trait. This is
because these regions are often found in the “noncoding” of the genome
regions.
The term “noncoding” describes how the genes in these regions do not immediately transfer – or “code” their genetic information to production
of proteins, which then fulfill a recognized biological function. That’s why
is still largely unknown which biological processes take place in these “non-
coding” areas.
We wanted to know what was going on in these areas, Won said. That’s why we created Hi-coupled MAGMA (H-MAGMA), a calculation tool, to
assist in our efforts to better understand the results of our genome-wide research.
In a previous study, Won’s lab showed how to use H-MAGMA to study
brain diseases can reveal the genes linked to it, as well as
their underlying biology.
Her lab also expanded the tool to include drinking alcohol and smoking cigarettes for this particular paper.
They created H-MAGMA frameworks of cortical neurons and dopaminergic
neurons, two classes of brain cells that have long been associated with substance abuse.
Won’s team, led by Sey, an HHMI Gilliam Fellow, focused on those two cell types and used H-MAGMA to analyze GWAS results related to heavy drinking, heavy smoking, nicotine addiction and problematic alcohol use to determine the genes that are responsible for each characteristic.
Genes linked to alcohol consumption and cigarette smoking were also linked to:
genes for cocaine and morphine use.
While the opioid epidemic has had a negative social impact, there are currently no well-researched GWAS on cocaine and opioid use.
Therefore, Won’s team examined whether the genes linked to alcohol consumption and cigarette smoking could provide insights into the genetics underlying general addiction behavior, and genetic discoveries that could be generalized to other addictive drugs.
Our research has shown that other substances, such as cocaine, can affect
the expression of genes associated with traits associated with cigarette smoking
and alcohol use, according to Won.
We will be able to determine the basic mechanisms behind addiction by describing the biological function of these genes, which can be generalized to different types of substance use disorders.
Won’s team also discovered other cell types, such as cortical glutamatergic,
dopaminergic, GABAergic, and serotonergic neurons in the midbrain that
associated with the risk genes, in addition to the different types of excitatory neurons.
With these results in hand, UNC researchers and others can now look at:
chemicals that significantly reduce the likelihood of addiction.
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