Genetic Indicators of High BMI in Childhood Linked to Higher MS Risk

Genetic variants that contribute to a high body mass index (BMI) during childhood are associated with an increased risk of developing multiple sclerosis (MS), a study found.

The relationship is likely influenced by the fact that a higher BMI in childhood is linked to obesity in adulthood and a “longer exposure” to high BMI throughout life, the researchers said.

The study, “Age-specific effects of childhood body mass index on multiple sclerosis risk,” was published in the Journal of Neurology. 

MS is thought to arise from a combination of genetic and environmental factors. Childhood obesity, marked by a high BMI, has been previously identified as a risk factor for developing the autoimmune disease.

But it’s not known if there is an exact age window during development wherein BMI influences this risk most significantly.

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A research team in the U.K. sought to learn more about this relationship by analyzing data from several large genome-wide association (GWAS) studies. GWAS studies collect genetic and clinical information from large groups of people — usually several thousand — to identify genetic changes, or variants, that are associated with a particular clinical feature. Here, the team used GWAS data related to childhood BMI and MS in adulthood.

Using information from the GWAS studies, researchers performed a Mendelian randomization (MR) analysis. This type of analysis uses the genetic signatures of a clinical trait, rather than the trait itself, to identify causal relationships between that trait and a later outcome.

In this case, the team evaluated the relationship between genetic signatures associated with high childhood BMI and the later development of MS.

The analyses included BMI data from more than 28,000 children, and data from more than 14,000 adults with MS and 26,000 adults without MS.

The research team collapsed childhood GWAS data into four developmental windows: birth (birth to 6 weeks),  infancy (3 months to 1.5 years), early childhood (2–5 years), and later childhood (7–8 years).

Genetic signatures of a higher BMI in infancy, early childhood, and later childhood were each correlated with an increased risk of developing MS in adulthood. Birth BMI was not associated with a higher MS risk.

This causal effect was shown to be likely dependent on the persistence of high BMI in adulthood. In other words, children with a high BMI are more likely to be overweight adolescents and adults, which could be the main driver of MS risk.

“It is plausible that a longer ‘exposure’ to high BMI — especially if this exposure coincides with the seemingly critical window during adolescence — is associated with higher MS risk,” the researchers wrote.

While it’s unclear what might be behind this association, obesity-associated inflammation and changes to microbes living in the gut could be involved, the researchers hypothesized.

“In summary, we provide evidence from longitudinal MR that the relationship between genetically determined early-life BMI and MS appears to follow a gradient, with no effect at birth and a gradually increasing influence on later-life MS risk,” the researchers wrote, adding that “this gradient may be accounted for by the effect of these genetic variants on BMI in adulthood.”

Further research is needed to determine whether there is indeed a critical time window in which elevated BMI increases MS risk, the researchers said.