Genome-Wide by Lifetime Environment Interaction Studies of Brain Imaging Phenotypes

Area of Science:

• Neuroscience
• Genetics
• Environmental Health

Background:

• Individual brain structure and function exhibit significant variation influenced by genes, environment, and their interactions.
• While genetic and environmental main effects are increasingly understood, gene-environment interactions on brain phenotypes remain largely unexplored.

Purpose of the Study:

• To investigate genome-wide by environment interactions across 41 exposures on 598 brain imaging phenotypes in a large cohort of healthy young adults.
• To identify specific gene-environment interactions and their contribution to brain phenotype variance.

Main Methods:

• Employed genome-wide association studies (GWAS) combined with environmental exposure data (exposome-wide).
• Utilized univariate and multivariate statistical analyses to detect significant gene-environment interactions.
• Conducted protein-protein interaction network analyses and pathway enrichment analyses.

Main Results:

• Identified 486 significant gene-environment interactions, surpassing the explanatory power of genetic and environmental main effects.
• Discovered variants enriched in regulatory regions and associated with brain gene expression.
• Revealed distinct interaction networks for air pollution and urbanicity exposures, with specific pathways implicated (e.g., metal ion detoxification).
• Identified 144 interactions with sensitive developmental periods in childhood and adolescence.

Conclusions:

• Genome-wide by exposome-wide interaction studies are crucial for understanding brain phenotype variability.
• Gene-environment interactions offer critical insights for optimizing brain health outcomes and developing targeted interventions.