{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:07:59Z","timestamp":1789967279839,"version":"4.0.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The epidemiological link between dry eye disease (DED) and chronic pain is established, yet a shared genetic etiology remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Utilizing GWAS summary data, we applied linkage disequilibrium score regression (LDSC) to determine genetic correlation between DED and multisite chronic pain (MCP). We investigated SNP enrichment across tissues using stratified LD score regression (S-LDSC) and multimarker analysis of genome annotation (MAGMA). Common risk SNPs were identified via Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC), followed by pleiotropic analysis under the composite null hypothesis (PLACO) and colocalization. Multi-trait colocalization (Hyprcoloc) integrating brain imaging-derived phenotypes (IDPs) was applied to explore neuroimaging mediators. We further investigated risk gene expression profiles using Summary-data-based Mendelian randomization (SMR) to explore functional genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found significant genetic correlation between DED and MCP, highlighting shared risk SNPs (rs13107325, rs7105462, rs7959961). Hyprcoloc revealed rs13107325 as a central hub with three-way colocalization across 95 IDPs. Partitioned analysis identified 11 functional elements associated with both phenotypes. Tissue enrichment converged on brain regions, notably the anterior cingulate cortex and cerebellar hemispheres. SMR identified 21 shared functional genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests genetic correlation and common risk genes between DED and MCP, advancing understanding of their pathogenesis and assisting in identifying therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1918770","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:28:57Z","timestamp":1789964937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the shared genetic architecture between dry eye disease and multisite chronic pain"],"prefix":"10.3389","volume":"13","author":[{"given":"Gangyi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Zigong First People's Hospital","place":["Zigong, 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