Genetics, environment may interact to affect early brain development
Early interventions that target risk factors may help mitigate MS development
An interplay between genetic and environmental risk factors, including tobacco smoke exposure, affects brain development in early childhood, which could increase the likelihood a person will develop multiple sclerosis (MS), according to a recent study.
Among young children in the Netherlands, being at a high genetic risk for MS, coupled with exposure to tobacco smoke in the household, was associated with lower brain volume on MRI scans. A high genetic risk for the disease was also linked to a heightened immune response against the Epstein-Barr virus (EBV), an established environmental risk factor for MS.
“Early-life environmental and genetic factors for MS influence brain development at an early age in the general population, highlighting the possibility for early interventions targeting modifiable risk factors to mitigate future MS development,” researchers wrote.
The study, “Environmental multiple sclerosis (MS) risk factors, genetic MS risk, and brain development in a general paediatric population,” was published in the Journal of Neurology, Neurosurgery, & Psychiatry.
MS thought to arise from combination of genetic, environmental risk factors
The exact cause of MS isn’t known, but it’s believed to arise from a combination of genetic and environmental risk factors. For example, several environmental risk factors, including past infection with EBV, low vitamin D levels, tobacco exposure, and obesity, have been associated with MS risk.
Also, while no specific gene mutation causes MS, researchers now understand that a combination of genetic risk factors can collectively make it more likely that a person will get MS. Scientists have developed risk scores to estimate a person’s susceptibility based on the presence of multiple genetic variants linked to the disease.
It isn’t exactly known when MS disease processes start, but it’s believed that early life exposure to environmental risk factors may affect brain development in ways that make MS more likely later on.
Still, exactly how this complex group of genetic and environmental risk factors might interact early in life to influence brain development is not established.
To learn more, scientists leveraged data from a large population-based study in the Netherlands that was designed to follow people through life, from birth to adulthood, to identify the environmental and genetic factors that influence development. Genetic data from 2,817 participants, and brain imaging data from 2,970 were used in the final analysis.
Participants, none of whom had been diagnosed with MS, had available genetic data that was used to calculate a risk score estimating their genetic susceptibility to the disease.
Data were also available on environmental factors including EBV infection, vitamin D levels, body mass index (a measure of body fat), tobacco exposure from parents who smoke, and outdoor activity at age 5. Children underwent MRI brain scans at ages 9 and 13.
Genetic risk factors for MS was associated with strong immune response to EBV
Results generally showed that, among EBV-positive children, being at a higher genetic risk for MS was associated with higher blood levels of anti-EBV antibodies, reflecting a stronger immune response against the virus.
The researchers suggested that genetic risk factors might make it harder for the immune system to control EBV, thereby further driving MS risk in infected people.
A higher genetic risk for MS was also associated with a lower volume of gray matter, or the brain tissue containing mostly cell bodies, in subcortical areas, or the tissues lying deeper in the brain.
In combined analyses considering both genetics and environment, the researchers found genetic risk and exposure to parental smoking interacted to influence brain volume. Particularly, parental smoke exposure along with a higher genetic risk score were associated with lower total brain volume, lower subcortical gray matter volume, and lower volume of a brain region called the thalamus.
“This indicates that a higher genetic MS risk is associated with an increased vulnerability to the negative effects of household smoking on brain development,” the researchers wrote.
It’s widely believed tobacco smoke may contribute to MS risk by increasing chronic inflammation. Early life exposure may affect the developing immune system, and when coupled with genetic risk factors, increases the likelihood of MS, according to the scientists.
Overall, identifying these relationships “may open a window for prevention of MS by limiting childhood exposure to household smoking or other toxic exposures associated with MS,” the researchers wrote.
Still, given the observational nature of the study, the findings are not enough to conclude that these risk factors ultimately cause the disease, the researchers noted. More research to explore these relationships will still be needed.
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