GWAS of Extended Prescription Analgesic Use Identifies Novel Genetic Loci in Chronic Pain

Pain-related conditions are the leading cause of disability worldwide. Current genome-wide association studies (GWAS) for chronic pain have mainly focused on individual pain-related disorders, which may not optimally capture the phenotype. Here, we applied a novel method of defining chronic pain based on prescription analgesic use ([≥]90 days) in two large biobanks (UK Biobank and FinnGen). GWAS meta-analyses of 11 prescription-based pain phenotypes identified 140 associations with chronic pain--78 novel (e.g. ARPP21, CNTNAP2) and 62 previously reported (e.g. SLC39A8, DCC, TRPM8). Integrating these genetic associations with functional data including transcriptome-wide association studies, cell-type and pathway enrichment, and gene enrichment in mouse phenotypes identified novel potential mechanisms involved in chronic pain, implicating oligodendrocyte differentiation, neuronal guidance, endolysosomal function and post-synaptic endosome recycling. Our study showcases how the use of prescription data to identify and characterize pain provides new insights into pain genetics and its underlying biology.