{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:12:17Z","timestamp":1787166737776,"version":"build-2736575974"},"posted":{"date-parts":[[2025,11,12]]},"group-title":"Respiratory Medicine","reference-count":102,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  We conducted the largest GWAS meta-analysis for obstructive sleep apnoea (OSA; N\n                  <jats:sub>cases<\/jats:sub>\n                  = 230,657; N\n                  <jats:sub>controls<\/jats:sub>\n                  = 1,377,442) using European ancestry genetic data from five countries. We identified 147 independent loci associated with OSA, and estimated SNP-based heritability at 16%. We report six independent loci in a separate African population meta-analysis (N\n                  <jats:sub>cases<\/jats:sub>\n                  = 46,834; N\n                  <jats:sub>controls<\/jats:sub>\n                  = 149,192). We observed spatially resolved gene enrichment involving GABAergic and glutamate pathways, synaptic transmission, and cytoskeletal remodelling. OSA-derived polygenic risk scores showed predictive ability for clinician ascertained OSA status, Fitbit-derived sleep features, and self-reported sleep traits in participants of diverse ancestral backgrounds. We identified putative causal relationships with ADHD, depression, multisite chronic pain, body mass index, and schizophrenia, among others. Our findings demonstrate a robust genetic component underlying OSA risk, independent of body mass index, implicating distinct neurobiological pathways related to synaptic function and corticothalamic feedback loops.\n                <\/jats:p>","DOI":"10.1101\/2025.11.08.25339824","type":"posted-content","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T23:45:12Z","timestamp":1762991112000},"source":"Crossref","is-referenced-by-count":1,"title":["Genome-wide analysis in over 1.6 million participants uncovers 147 loci associated with obstructive sleep apnoea"],"prefix":"10.64898","author":[{"given":"Luis M.","family":"Garc\u00eda-Mar\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuriel","family":"Ceja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abishna","family":"Parasuraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Wen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"D\u00edaz-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Flores-Ocampo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma M.","family":"Aman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateo","family":"Maya-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura","family":"Aguilar-Rold\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bade","family":"Uckac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia S.","family":"Ogonowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"MacGregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-9320","authenticated-orcid":false,"given":"Xianjun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-6890","authenticated-orcid":false,"given":"Sarah J.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Seviiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-7248","authenticated-orcid":false,"given":"Miguel E.","family":"Renter\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025111400351058000_2025.11.08.25339824v1.1","unstructured":"Slowik, J. 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