Genome-wide analysis identifies significant contribution of brain-expressed genes in chronic, but not acute, back pain

Back pain is the leading cause of disability worldwide. Although most cases of back pain are acute, 20% of people with acute back pain go on to experience chronic back pain symptoms. It is unclear if acute and chronic pain states have similar or distinct underlying genetic mechanisms. Here we performed a genome-wide analysis for acute and chronic back pain in 375,158 individuals and found a significant genetic contribution to chronic, but not to acute, back pain. Using the UK Biobank cohort for discovery and the HUNT cohort for replication, we identified 7 loci for chronic back pain, of which 3 are novel. Pathway analyses, tissue-specific heritability enrichment analyses, epigenetic characterization, and tissue-specific transcriptome mapping in mouse pain models suggest a substantial genetic contribution to chronic, but not acute, back pain from the loci predominantly expressed in the central nervous system. Our findings show that chronic back pain is more heritable than acute back pain and is driven mostly by genes expressed in the central nervous system.