Media release

From: BMJ Group

Cutting early life exposure to parental smoking may lower MS risk in genetically prone

Interplay of genes + environment alter key aspects of brain structure at young age, boosting susceptibility

Cutting early life exposure to parental smoking may lower the risk of developing MS (multiple sclerosis) in those who are genetically predisposed to the disease, finds research published online in the Journal of Neurology Neurosurgery & Psychiatry.

The interplay of genes and environmental factors, including smoking, alter key aspects of brain structure in early childhood, likely facilitating development of the disease and suggesting that there may be a window of opportunity to stave this off, conclude the researchers.

MS is an autoimmune disease that is typically diagnosed between the ages of 20 and 40. But it’s not clear if it stems from early inflammatory brain damage or a latent neurodegenerative process overlaid with inflammation, explain the researchers.

Exactly when the disease process begins isn’t known either. But brain volume loss and poorer cognitive performance before clinical signs and symptoms appear suggests that these precede diagnosis.

Studies on migration show that early life environmental factors have a key role, but exactly how these interact isn’t yet known, they add.

To shed more light on how and when the interplay of environmental and genetic risk factors might affect brain volume, and so facilitate future MS development, the researchers used data from the population based Dutch Generation R study.

Participants in this study had good quality data on genotype and/or the known environmental risk factors of Epstein Barr virus infection, vitamin D levels, weight (BMI), parental tobacco exposure, and outdoor activity at the age of 5, plus high quality brain scan images at the ages of 9 and 13.

In all, the researchers drew on imaging data showing brain volume for 5350 participants and brain microstructure for 5649 participants, none of whom had been diagnosed with MS.

Polygenic risk scores, derived from DNA samples, were used to assess genetic risk of developing MS, with the genetic variant rs10191329, used as a marker of future MS severity.

In all, 642 children tested positive for Epstein Barr virus infection and 405 had been exposed to household parental smoking.

The final analysis was based on genetic data from 2817 participants and brain volume and microstructure imaging data from 2970 participants.

This showed an interplay between genetic and environmental risk factors for MS that was associated with certain aspects of brain structure during childhood and the early teens.

Specifically, higher genetic risk for MS was associated with a strong immune response to Epstein-Barr virus infection, and it was also associated with increased susceptibility to the negative effects of household parental smoking on brain development.

Higher MS genetic risk and household parental smoking interacted and were associated with lower total brain volume and grey matter volume, including thalamic volume.

No associations were observed for carriers of the rs10191229 genetic valiant.

This is an observational study, and as such, no firm conclusions about cause and effect can be drawn.

By way of explanations for the findings, the researchers point out that higher Epstein-Barr virus antibodies may be caused by defective immune system control of this virus due to genetic risk for MS, possibly facilitating development of the disease later in life.

And the prevailing theory is that tobacco smoke produces chronic inflammation of the respiratory tract, thereby increasing the inflammatory activity of the immune system, they add.

“Our results importantly add another potential mechanism of tobacco smoke exposure in individuals with higher polygenic MS risk. The increased brain vulnerability to the effects of parental smoking may increase exposure of [central nervous system] antigens to the developing immune system, increasing the risk of a brain specific autoimmune disease,” they suggest.

“How this increased vulnerability influences other MS risk factors may open a window for prevention of MS by limiting childhood exposure to household smoking or other toxic exposures associated with MS (ie, household chemicals), and should be a focus for further studies,” they conclude.