Structural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities

Area of Science:

• Neurogenetics
• Cognitive Neuroscience
• Medical Imaging

Background:

• Genetic variance in brain structure and cognitive function is shared.
• Genome-wide association studies (GWA) provide insights into genetic underpinnings of complex traits.
• Polygenic scores (PS) aggregate effects of many genetic variants.

Purpose of the Study:

• To estimate polygenic scores for five brain magnetic resonance imaging (MRI) traits.
• To predict brain MRI traits and cognitive abilities using these polygenic scores.
• To investigate the genetic overlap between brain structure and cognitive function.

Main Methods:

• Utilized genetic association data from GWA meta-analyses for brain infarcts, white matter hyperintensities, intracranial volume, hippocampal volume, and total brain volume.
• Calculated polygenic scores for these five MRI traits in three Scottish cohorts (GS:SFHS, LBC1936, LBC1921).
• Assessed prediction of MRI traits in LBC1936 and cognitive traits across all cohorts.

Main Results:

• Polygenic prediction of intracranial volume was observed in the LBC1936 cohort.
• A significant negative correlation was found between hippocampal volume polygenic scores and global cognitive ability measures in the Lothian Birth Cohorts.
• The strength of associations varied, suggesting potential demographic influences on prediction accuracy.

Conclusions:

• Genetic influences on brain structure traits are partially shared with cognitive abilities.
• Polygenic scores can predict certain brain MRI traits and show correlations with cognitive measures.
• Further research in larger, well-matched samples is needed to confirm findings and explore genetic relationships between brain structure and cognition.