Neuroanatomical correlates of genetic risk for obesity in children

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Obesity has increased rapidly in recent decades to affect more than 2 billion people, making it one of the largest contributors to poor health worldwide. Despite decades of research on diet and exercise treatments, many people continue to struggle to lose weight.

Several teams think that molecular mechanisms of brain development during early life are likely a major determinant of obesity risk, in other words that obesity is a neurodevelopmental disorder.

Indeed obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system.

At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, authors from McGill University, Montréal, Canada, use a large sample of participants (n>4,000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral differences in adolescents.

In a series of analyses, the authors show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values.

Relatedly, using structural equation modeling, the authors find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI one year later.

In summay, authors' study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

Indeed the risk for obesity among children with a high genetic susceptibility also varies with environmental and sociodemographic factors during childhood. While all children benefit from an environment that supports a healthy lifestyle, they are particularly important for children with a high genetic risk for obesity.

Read the original article on medRxiv

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