{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:23:48Z","timestamp":1787793828171,"version":"build-2784847793"},"posted":{"date-parts":[[2026,3,30]]},"group-title":"Genetics","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health","award":["NIH, U19CA203654 (CIA, YH, JB)"],"award-info":[{"award-number":["NIH, U19CA203654 (CIA, YH, JB)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Genetic regulation of splicing uniquely contributes to trait-associated genome-wide association studies (GWAS) signals. However, quantitative trait loci (QTL) analysis using short-read sequencing of bulk tissues fails to capture full-length and cell-type-specific isoforms. Here, we present an isoform-level lung cell atlas from 129 never-smoking Korean women using single-cell long-read RNA-sequencing, identifying abundant unannotated and cell-type-specific isoforms. Isoform-level signatures of 37 lung cell types display a larger difference and therefore improve cell-type classification compared to gene-level expression. Notably, isoform-QTLs (isoQTLs) detect unannotated and\/or cell-type-specific isoforms with independent genetic regulation from expression-QTL (eQTL), supported by enriched splicing functional elements. IsoQTLs nominate susceptibility isoforms from previously unexplained lung function and cancer GWAS loci, via eQTL-independent signals. We highlight a potentially functional novel variant of\n                  <jats:italic>PPIL6<\/jats:italic>\n                  in multiciliated cells underlying lung cancer risk through alternative splicing. This isoform-level resource advances our understanding of cell-type-specific isoform regulation and its contribution to lung traits and diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.03.27.714873","type":"posted-content","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T01:25:17Z","timestamp":1774920317000},"source":"Crossref","is-referenced-by-count":1,"title":["Single-cell full-length transcriptome of human lung reveals genetic effects on isoform regulation beyond gene-level expression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-7107","authenticated-orcid":false,"given":"Bolun","family":"Li","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thong","family":"Luong","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and 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