1066 A Transcriptome-Wide Association Study Identifies Novel Genes and Therapeutic Targets for Cervical Myelopathy

INTRODUCTION: Cervical myelopathy is a degenerative spinal condition that can lead to severe neurological dysfunction. Despite its degenerative pathophysiology, family history has shown to be a largely important factor in incidence and progression, suggesting that inherent genetic predisposition may play a role in pathophysiology. METHODS: In a large, diverse, urban biobank of 32,031 individuals, with 558 individuals with cervical myopathy, we applied transcriptomic imputation to identify genetically regulated gene expression signatures associated with cervical myelopathy. We performed drug-repurposing analysis using the CMAP database to identify candidate therapeutic interventions to reverse the cervical myopathy-associated gene signature. RESULTS: We identified 16 genes significantly associated with cervical myelopathy across five different tissues, suggesting tissue-specific manifestations of inherited genetic risk. Drug repurposing identified 22 compounds that reversed the cervical myelopathy-associated signature, suggesting points of therapeutic intervention. CONCLUSIONS: The inherited genetic risk for cervical myelopathy is functionally mediated through genes involved in tissue-specific nociceptive and proliferative processes.