MONTRÉAL, February 19, 2024 – A new population-based study led by CHU Sainte-Justine Researcher Tomas Paus reveals the respective roles of maternal and fetal genes in the growth of a baby’s cerebral cortex. The results, published in the prestigious journal Nature Communication, show that genetic variants associated with higher birth weight are also associated with greater growth of the cerebral cortex. However, food abundance or scarcity seems to influence the extent of the role played by these genes.

Genes that make babies - and their brains - grow

With postdoctoral fellow Daniel Vosberg, Tomas Paus analyzed birth weight, birthweight genes and brain magnetic resonance imaging (MRI) data from several thousand adults in the UK Biobank, a biomedical database in the United Kingdom. These analyses confirmed that higher birth weight is associated with larger cortex size (measured by surface area). In addition, the genetic variants present in the mother and baby that are associated with birthweight are also associated with cortical surface. In the baby, genes associated with insulin action are decisive, while in the mother, genetic variants favouring toxin elimination at the cellular level play a major role.

Impact of food availability and intergenerational transmission

The two groups of genetic variants are not always equally important in determining cortex size. “By comparing data by birth year and using statistical modelling and cellular interaction analysis, we’ve demonstrated the role of exposure to food restriction during gestation or infancy,” explained Tomas Paus, who is also a professor at Université de Montréal.

In the people exposed to food restriction (during the Second World War), maternal detoxification genes had the greatest impact on cortical growth. This trait seems to be transmitted from one generation to the next, since the association is also found in the children of people who were exposed to food restriction during the war. In others, cortical growth is mainly associated with genes associated with fetal insulin action.

The analyses suggest that the genes that counteract the negative effects of food restriction, particularly in terms of cellular stress and immune activation, are critical. “In times of famine, when cells are multiplying, the risk of errors is much greater,” explained the researcher. “That could explain why, in this context, the genes responsible for DNA repair are decisive for the baby’s brain growth.” 

Promoting brain growth from the earliest stages of life

Now that we have a better understanding of the relationship between low birth weight and brain growth, and the importance of malnourishment as a mediating factor, the next step is to evaluate the best way to promote cortical growth after birth in small babies. “In collaboration with CHU Sainte-Justine’s Dr. Thuy Mai Luu, we’ll soon be launching a pilot project to determine the best way to support optimal brain development in low-birth-weight babies,” said Tomas Paus.

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