{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:12:22Z","timestamp":1789521142030,"version":"build-2803163510"},"posted":{"date-parts":[[2026,2,6]]},"group-title":"Genetic and Genomic Medicine","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  We conducted the first genome-wide association meta-analyses of global and sectoral peripapillary retinal nerve fibre layer (pRNFL) thickness and Bruch\u2019s membrane opening-minimum rim width (BMO-MRW), the major optic nerve head structural and neurodegeneration biomarkers, including up to 25,942 and 12,080 participants, respectively, from the International Glaucoma Genetics Consortium. We identified 9 global pRNFL thickness and 9 global BMO-MRW loci, along with 28 and 19 loci for pRNFL and BMO-MRW sectors, respectively, comprising both shared and sector-specific loci. To identify intraocular pressure (IOP)-independent drug targets, global pRNFL thickness and BMO-MRW were conditioned on IOP. IOP-independent loci were then prioritised to identify candidate causal genes using transcriptome-wide association study and colocalization analysis. Several genes, such as\n                  <jats:italic>NMNAT2<\/jats:italic>\n                  and\n                  <jats:italic>TRIOBP,<\/jats:italic>\n                  had robust associations with both phenotypes, with potential IOP-independent therapeutic translation for glaucoma. Overall, we identified novel loci for pRNFL thickness and BMO-MRW, highlighting potential drug-target genes acting independently from IOP, and elucidating genetic differences among pRNFL sectors.\n                <\/jats:p>","DOI":"10.64898\/2026.02.03.26345426","type":"posted-content","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:50:11Z","timestamp":1770403811000},"source":"Crossref","is-referenced-by-count":1,"title":["Uncovering the Genetic Architecture of Optic Nerve Integrity Estimates through Genome-wide Association Study Meta-analyses"],"prefix":"10.64898","author":[{"given":"Asma M.","family":"Aman","sequence":"first","affiliation":[{"name":"QIMR Berghofer, Brisbane, Queensland, Australia"},{"name":"Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, 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