{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:24:43Z","timestamp":1785867883025,"version":"3.56.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Basal cell carcinoma (BCC), the most common skin cancer, is driven by UV-induced DNA damage and shaped by immune surveillance. Although GWAS has identified over 140 risk loci, their cell-type-specific effects remain obscured by tissue-level averaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated BCC GWAS summary statistics from a UK-based cohort (17,416 cases, 375,455 controls) with single-cell expression quantitative trait locus (sc-eQTL) data from 12 immune cell types in the OneK1K resource. Using the OTTERS framework combined with ACAT-O, we performed single-cell transcriptome-wide association analysis (scTWAS); bulk TWAS using GTEx whole blood served as a conventional tissue-averaged benchmark for comparison, rather than a definitive gold standard. Functional enrichment was conducted via Gene Ontology (GO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bulk TWAS using GTEx whole blood identified 35 BCC-associated genes (FDR\u2009&lt;\u20090.05), including\n                      <jats:italic>MC1R<\/jats:italic>\n                      and\n                      <jats:italic>CASP8<\/jats:italic>\n                      . In contrast, single-cell transcriptome-wide association study (scTWAS) across 12 OneK1K cell types revealed 207 non-redundant susceptibility genes, predominantly in CD4\n                      <jats:sub>ET<\/jats:sub>\n                      , MONO\n                      <jats:sub>C<\/jats:sub>\n                      , and B\n                      <jats:sub>IN<\/jats:sub>\n                      . Functional enrichment uncovered cell-type-specific programs: MHC class II antigen presentation (CD4\n                      <jats:sub>ET<\/jats:sub>\n                      ), PRR-mediated innate immunity (MONO\n                      <jats:sub>C<\/jats:sub>\n                      ), and pro-inflammatory secretion (B\n                      <jats:sub>IN<\/jats:sub>\n                      )\u2014all absent in bulk results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our exploratory scTWAS using healthy donor PBMC-derived eQTLs uncovered cell-type-specific BCC associations missed by bulk analyses, providing hypothesis-generating insights into immune-related genetic effects in BCC. This underscores how single-cell resolution can overcome signal dilution from cellular heterogeneity, though validation in tumor-derived immune populations is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0354887","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:22:06Z","timestamp":1785864126000},"page":"e0354887","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging expression quantitative trait loci information in single-cell resolution to identify cell-specific genes for Basal cell carcinoma"],"prefix":"10.1371","volume":"21","author":[{"given":"Min","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-0685","authenticated-orcid":true,"given":"Xiuqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"5","key":"pone.0354887.ref001","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/bjd\/ljae258","article-title":"COL10A1 expression distinguishes a 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