{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T12:21:43Z","timestamp":1794399703517,"version":"4.9.0"},"posted":{"date-parts":[[2026,3,23]]},"group-title":"Genomics","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["ASAP-000301"],"award-info":[{"award-number":["ASAP-000301"]}],"id":[{"id":"https:\/\/ror.org\/03zj4c476","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ASAP-024434"],"award-info":[{"award-number":["ASAP-024434"]}],"id":[{"id":"https:\/\/ror.org\/03zj4c476","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Yale School of Medicine\u0092s Stephen & Denise Adams Center for Parkinson\u0092s Disease Research"},{"name":"Yale American Parkinson Disease Association Center for Parkinson Precision Medicine","id":[{"id":"https:\/\/ror.org\/04sedwh45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Lineberger Research Fund"},{"award":["R01NS115144"],"award-info":[{"award-number":["R01NS115144"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HG012467"],"award-info":[{"award-number":["R01HG012467"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U24 NS072026"],"award-info":[{"award-number":["U24 NS072026"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 AG019610"],"award-info":[{"award-number":["P30 AG019610"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AG072980"],"award-info":[{"award-number":["P30AG072980"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]},{"award":["05700"],"award-info":[{"award-number":["05700"]}],"id":[{"id":"https:\/\/ror.org\/01smpj292","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Arizona Biomedical Research Commission","award":["4001"],"award-info":[{"award-number":["4001"]}]},{"name":"Arizona Biomedical Research Commission","award":["0011"],"award-info":[{"award-number":["0011"]}]},{"name":"Arizona Biomedical Research Commission","award":["05-901"],"award-info":[{"award-number":["05-901"]}]},{"name":"Arizona Biomedical Research Commission","award":["1001"],"award-info":[{"award-number":["1001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,11,11]]},"abstract":"<jats:p>Structural variants (SVs) are a major source of genetic diversity, yet how they impact cell types in complex brain diseases remains largely unexplored, partially due to limitations of short-read sequencing. Here, we addressed this fundamental question in Parkinson's disease (PD). generating long-read whole-genome sequencing (WGS) data for 100 post-mortem brain samples from a PD cohort, constructing a high-confidence catalog of 74,552 SVs. To resolve their functional impact, we integrated single-nucleus RNA-sequencing data from two brain regions from the same samples and focused functional analyses on SVs proximal to genes previously nominated as cis-regulated, potential causal targets of PD-associated GWAS loci. Using expression quantitative trait locus and allele-specific expression analyses, we uncovered SVs significantly associated with expression in specific cell types as well as effects shared across cell types. This study demonstrates the power of uniting long-read WGS with transcriptomics to uncover SVs underlying complex disease architecture with cell type resolution.<\/jats:p>","DOI":"10.64898\/2026.03.20.713192","type":"posted-content","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:45:16Z","timestamp":1774331116000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrating Long-Read Structural Variant Analysis with single-nucleus RNA-seq to Elucidate Gene Expression Effects in Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-3193","authenticated-orcid":false,"given":"Kwanho","family":"Kim","sequence":"first","affiliation":[{"name":"Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD  20815, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA  02142, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-5194","authenticated-orcid":false,"given":"Zechuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD  20815, USA; Stephen & Denise Adams Center for Parkinson's Disease Research of Yale School of Medicine, New Haven, CT  06510, USA; APDA Center for Parkinson Precisi;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-4000","authenticated-orcid":false,"given":"Sean K","family":"Simmons","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD  20815, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA  02142, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-6418","authenticated-orcid":false,"given":"Jacob","family":"Parker","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD  20815, USA; Stephen & Denise Adams Center for Parkinson's Disease Research of Yale School of Medicine, New Haven, CT  06510, USA; 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