Investigating the Shared Genetic Architecture Between Psychiatric Disorders and Executive Function.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Executive functions (EF) are frequently comorbid with psychiatric disorders, suggesting shared underlying pathophysiology.
• The genetic basis of this comorbidity, particularly the shared genetic architecture between psychiatric disorders and EF, is not well understood.

Purpose of the Study:

• To systematically investigate the shared genomic architectures between major psychiatric disorders and executive function.
• To identify common genetic loci and biological mechanisms contributing to the comorbidity of psychiatric disorders and EF.

Main Methods:

• Utilized large genome-wide association study datasets for bipolar disorder, major depressive disorder, and schizophrenia from the Psychiatric Genomics Consortium and iPSYCH.
• Employed a common factor of EF from UK Biobank, alongside statistical genetic, functional genomic, and gene-level analyses.

Main Results:

• Demonstrated substantial genetic overlaps and significant genetic correlations between psychiatric disorders and EF.
• Identified numerous shared genomic loci and phenotype-influencing variants, with enrichment suggesting frontal cortex and prefrontal glutamatergic neuron involvement.
• Functional genomic analyses revealed regulatory variants impacting transcription factor binding and identified shared genes related to synaptic processes and fetal brain development.

Conclusions:

• Provided strong evidence for extensive shared genetic architectures between psychiatric disorders and EF.
• Findings have significant implications for future research into the mechanisms of these disorders and for the development of novel therapeutic strategies and drug development efforts.