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Drug-Gene Pairs That May Target Shared Psychiatric Risk Pathways Identified
A genetic association study has revealed 466 genes related to genomic factors that index shared risk across subsets of psychiatric disorders. Researchers published their findings in JAMA Psychiatry.
“Psychiatric disorders display high levels of comorbidity and genetic overlap, necessitating multivariate approaches for parsing convergent and divergent psychiatric risk pathways,” wrote first author Andrew D. Grotzinger, PhD, of the University of Colorado Boulder, and study coauthors. “Identifying gene expression patterns underlying cross-disorder risk also stands to propel drug discovery and repurposing in the face of rising levels of polypharmacy.”
The study used transcriptome-wide structural equation modeling to look at gene expression patterns linked with 5 genomic factors indexing shared risk across 13 major psychiatric disorders.
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“In total, T-SEM identified 466 genes whose expression was significantly associated (z ≥ 5.02) with genomic factors and 36 genes with disorder-specific effects,” researchers reported. “Most associated genes were found for a thought disorders factor, defined by bipolar disorder and schizophrenia.”
Using public databases of drug-gene pairs to investigate whether existing drugs could be repurposed to target genes linked with cross-disorder risk, the investigators found several possible options associated with the thought disorders factor or a transdiagnostic p factor for all 13 disorders.
“Results revealed 35 drug-gene pairs that may target shared risk pathways across bipolar disorder and schizophrenia,” researchers wrote, “and 5 drug-gene [pairs] with potential transdiagnostic effect.”
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