{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T19:42:09Z","timestamp":1776541329299,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,16]]},"group-title":"Orthopedics","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Osteoarthritis (OA) is a prevalent musculoskeletal disorder and a leading cause of global disability. Although meniscal damage is a major risk factor of OA pathogenesis, genetic regulatory studies have remained largely confined to articular cartilage. Here, we establish the first comprehensive expression quantitative trait locus (eQTL) map integrating whole-genome sequencing and bulk transcriptomics from human meniscus (n=112) and cartilage (n=113). Supported by single-nucleus multiomics (cartilage: 56,549 nuclei; meniscus: 34,343 nuclei), we uncovered highly tissue-specific genetic risk architectures. Colocalization with OA GWAS identified 27 meniscus-specific, 28 shared, and 20 cartilage-specific causal genes. Chromatin-informed fine-mapping and deconvolution elucidated distinct pathogenic mechanisms; notably, meniscus-specific signals converged on\n                  <jats:italic>VEGFA<\/jats:italic>\n                  via rare promoter variants and an enhancer in fibrochondrocyte progenitors, alongside a shared eQTL for\n                  <jats:italic>CLEC18A<\/jats:italic>\n                  . Exploratory analysis suggested candidate compounds to reverse pathogenic gene expression. Our findings underscore the meniscus as a distinct genetic driver, molecularly reinforcing OA as an entire joint organ failure.\n                <\/jats:p>","DOI":"10.64898\/2026.04.12.26350702","type":"posted-content","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:05:11Z","timestamp":1776384311000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated mapping of human meniscus and cartilage eQTLs reveals shared and distinct osteoarthritis genetic drivers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-6879","authenticated-orcid":false,"given":"Yutaro","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, The Scripps Research Institute"},{"name":"Department of Systems Biomedicine, Institute of Science 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