{"doi":"10.1101/2025.09.29.25336894","title":"Multi-ancestral genome-wide study of chronic pain reveals widespread genetic correlations with mental and physical health traits","abstract":"Abstract Chronic pain (CP) is a debilitating condition that impacts an individual’s 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 N case = 137 043, total N control = 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 (r g = 0.69, p = 1.82E-69), generalized addiction risk (r g = 0.39, p = 1.98E-18), and increased serum C-reactive protein levels (r g = 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. Highlights 48.8% of individuals were recorded as having a lifetime incidence of chronic pain. One locus, rs5795684, was significant in individuals of admixed ancestry. One additional locus, rs1196962975, was significant in a cross-ancestral meta-analysis. Genetic associations were enriched in brain areas such as the nucleus accumbens and amygdala. Chronic pain was moderately to highly genetically correlated to other physical and psychiatric health traits.","journal":"medRxiv","year":2025,"id":576356,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":0.0,"corpus_rank":10062,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":743728,"name":"Jared V. Balbona","orcid":"0000-0003-4466-248X","position":1,"is_corresponding":false},{"id":1485270,"name":"Nithya Sarabudla","orcid":null,"position":2,"is_corresponding":false},{"id":230692,"name":"Alexander S. Hatoum","orcid":"0000-0002-8002-7267","position":3,"is_corresponding":false},{"id":292133,"name":"Simon Haroutounian","orcid":"0000-0003-2231-5452","position":4,"is_corresponding":false},{"id":230004,"name":"Arpana Agrawal","orcid":"0000-0002-0313-793X","position":5,"is_corresponding":false},{"id":230001,"name":"Emma C. Johnson","orcid":"0000-0003-0394-777X","position":6,"is_corresponding":false},{"id":1120911,"name":"Pamela N Romero Villela","orcid":"0000-0002-6401-3260","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:57:56.636458Z","pmid":"41256146","pmcid":"PMC12622132","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}