Multi-ancestral genome-wide study of chronic pain reveals widespread genetic correlations with mental and physical health traits

Chronic pain (CP) is a debilitating condition that impacts an individuals physical and mental health. CP is common, affecting around 12-40% of individuals across the world. In this study, we conducted a genome-wide association study (GWAS) of lifetime incidence of CP in the All of Us Research Program, across six different ancestries in the United States (total Ncase = 137 043, total Ncontrol = 154 038). We found one genome-wide significant locus in the cross-ancestry meta-analysis on chromosome 5 (lead SNP: rs1196962975, p = 4.53E-08). Additionally, one locus on chromosome 11 (lead SNP: rs5795684) reached genome-wide significance in the admixed genetic ancestry sample (p = 1.13E-08). Cross-ancestry genetic correlations ranged from 0.40 - 0.78. CP was genetically correlated with a range of psychiatric, physical health, and immune traits, including anxiety (rg = 0.69, p = 1.82E-69), generalized addiction risk (rg = 0.39, p = 1.98E-18), and increased serum C-reactive protein levels (rg = 0.35, p = 5.28E-22). This study represents the largest cross-ancestral investigation of the genetics of lifetime incidence of chronic pain to date and demonstrates shared genetic effects between chronic pain and psychiatric disorders and other physical health conditions. HighlightsO_LI48.8% of individuals were recorded as having a lifetime incidence of chronic pain. C_LIO_LIOne locus, rs5795684, was significant in individuals of admixed ancestry. C_LIO_LIOne additional locus, rs1196962975, was significant in a cross-ancestral meta-analysis. C_LIO_LIGenetic associations were enriched in brain areas such as the nucleus accumbens and amygdala. C_LIO_LIChronic pain was moderately to highly genetically correlated to other physical and psychiatric health traits. C_LI