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Prefrontal gray matter volume mediates genetic risks for obesity.

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  • 1Department of Psychiatry, University of Münster, Münster, Germany.

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Genetic predisposition and brain structure are linked to obesity. Reduced medial prefrontal gray matter mediates the effect of polygenic obesity risk on body mass index (BMI), suggesting potential imaging biomarkers for clinical use.

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Area of Science:

  • Neuroscience
  • Genetics
  • Obesity Research

Background:

  • Neuroimaging and genetic studies have identified biological factors associated with obesity.
  • An integrated model linking genetic risk and brain structure in obesity pathophysiology is lacking.

Purpose of the Study:

  • To investigate the relationship between polygenic risk for obesity, gray matter structure, and body mass index (BMI).
  • To explore the mediating role of prefrontal gray matter in the genetic influence on BMI.
  • To assess the potential of brain imaging for predicting BMI.

Main Methods:

  • Utilized univariate and multivariate analyses in two independent cohorts (n=330, n=347).
  • Examined associations between polygenic risk scores, BMI, and gray matter volume.
  • Employed multivariate pattern classification for BMI prediction using whole-brain imaging data.

Main Results:

  • Higher BMI and polygenic obesity risk correlated with decreased medial prefrontal gray matter in both cohorts.
  • Medial prefrontal gray matter significantly mediated the impact of polygenic obesity risk on BMI.
  • Individual BMI prediction was successful using whole-brain imaging data, validated in an independent cohort.

Conclusions:

  • Establishes a link between genetic predisposition, prefrontal gray matter structure, and BMI.
  • Suggests medial prefrontal gray matter as a key mediator in obesity pathophysiology.
  • Highlights the potential of neuroimaging markers for clinical applications in obesity management.