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    Area of Science:

    • Neuroimaging Genetics
    • Developmental Neuroscience
    • Computational Neuroscience

    Background:

    • Understanding the interplay between genetics, brain structure, and function is crucial for neurodevelopmental research.
    • Previous studies have explored these relationships, but causal pathways remain complex and require further investigation.

    Purpose of the Study:

    • To investigate the mediating role of structural connectivity (SC) in linking genetic variations (single nucleotide polymorphisms - SNPs) to brain functional connectivity (FC).
    • To explore these relationships across neurodevelopment using a causal mediation framework.

    Main Methods:

    • Utilized data from the Adolescent Brain Cognitive Development (ABCD) study, including SC, FC, and ~500k SNPs from 11,666 subjects.
    • Employed genome-wide association studies (GWAS) to identify SNPs associated with SC and FC traits.
    • Conducted mediation analyses to determine direct and indirect genetic effects on brain networks via SC.

    Main Results:

    • Identified specific SNPs directly influencing brain functional networks.
    • Revealed that structural connectivity mediates the indirect impact of certain genetic exposures on functional connectivity.
    • Demonstrated how genetic variations shape both structural and functional brain network organization.

    Conclusions:

    • Genetic variations significantly influence brain structural and functional network organization during neurodevelopment.
    • Structural connectivity plays a key mediating role in the genetic architecture of brain function.
    • This research provides deeper insights into the causal pathways linking genetic factors to large-scale brain networks.