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GWAS meta-analysis reveals dual neuronal and immunological etiology for pain susceptibility

By Evelina Mocci, Kathryn Ward, Susan G Dorsey, Seth A Ament

Posted 26 Aug 2021
medRxiv DOI: 10.1101/2021.08.23.21262510

Chronic pain is at epidemic proportions in the United States, represents a significant burden on our public health system and is coincident with a growing opioid crisis. While numerous genetic risk factors have been identified, its genetic basis remains poorly understood. Here, we conducted a meta-analysis of genome-wide association study (GWAS) summary statistics from seventeen pain susceptibility traits in the UK Biobank. This analysis revealed 99 genome-wide significant risk loci, of which 62 have not been previously associated with a pain-related trait. Risk loci were enriched for genes involved in neurological and inflammatory pathways. Two-sample Mendelian randomization indicated that depression, neuroticism, and immunological traits mediate many of these effects. These analyses double the number of known risk loci for pain susceptibility and support dual causation from neuronal and immunological genes, providing leads toward targets for novel pain medications.

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