{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:09:01Z","timestamp":1768572541643,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,30]]},"group-title":"Genetic and Genomic Medicine","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic pain (CP) is a debilitating condition that impacts an individual\u2019s 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\n                  <jats:sub>case<\/jats:sub>\n                  = 137 043, total N\n                  <jats:sub>control<\/jats:sub>\n                  = 154 038). We found one genome-wide significant locus in the cross-ancestry meta-analysis on chromosome 5 (lead SNP: rs1196962975,\n                  <jats:italic>p<\/jats:italic>\n                  = 4.53E-08). Additionally, one locus on chromosome 11 (lead SNP: rs5795684) reached genome-wide significance in the admixed genetic ancestry sample (\n                  <jats:italic>p<\/jats:italic>\n                  = 1.13E-08). Cross-ancestry genetic correlations ranged from 0.40 \u2013 0.78. CP was genetically correlated with a range of psychiatric, physical health, and immune traits, including anxiety (r\n                  <jats:sub>g<\/jats:sub>\n                  = 0.69,\n                  <jats:italic>p<\/jats:italic>\n                  = 1.82E-69), generalized addiction risk (r\n                  <jats:sub>g<\/jats:sub>\n                  = 0.39,\n                  <jats:italic>p<\/jats:italic>\n                  = 1.98E-18), and increased serum C-reactive protein levels (r\n                  <jats:sub>g<\/jats:sub>\n                  = 0.35,\n                  <jats:italic>p<\/jats:italic>\n                  = 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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>48.8% of individuals were recorded as having a lifetime incidence of chronic pain.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>One locus, rs5795684, was significant in individuals of admixed ancestry.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>One additional locus, rs1196962975, was significant in a cross-ancestral meta-analysis.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Genetic associations were enriched in brain areas such as the nucleus accumbens and amygdala.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Chronic pain was moderately to highly genetically correlated to other physical and psychiatric health traits.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.29.25336894","type":"posted-content","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T20:05:13Z","timestamp":1759262713000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-ancestral genome-wide study of chronic pain reveals widespread genetic correlations with mental and physical health traits"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-3260","authenticated-orcid":false,"given":"Pamela N","family":"Romero Villela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-248X","authenticated-orcid":false,"given":"Jared V","family":"Balbona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9126-6885","authenticated-orcid":false,"given":"Nithya","family":"Sarabudla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-7267","authenticated-orcid":false,"given":"Alexander S","family":"Hatoum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-5452","authenticated-orcid":false,"given":"Simon","family":"Haroutounian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-793X","authenticated-orcid":false,"given":"Arpana","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0394-777X","authenticated-orcid":false,"given":"Emma C","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025100301550927000_2025.09.29.25336894v1.1","unstructured":"Merskey H . 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