{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:07:40Z","timestamp":1788883660082,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Objective<\/jats:title>\n Meniere\u2019s disease is a disabling inner-ear disorder whose molecular basis remains poorly understood. Immune dysregulation and genetic susceptibility have been implicated in disease etiology, but the genes and immune-cell programs linking genetic susceptibility to disease-associated molecular alterations remain incompletely defined. Focusing on zinc transport and immune signaling, we aimed to prioritize genetically supported candidate genes and identify the immune-cell programs in which they are embedded.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We combined bulk peripheral blood transcriptomes, single-cell RNA sequencing of peripheral blood mononuclear cells, large-scale blood eQTL data, and genome-wide association summary statistics for Meniere\u2019s disease. Differential expression analysis and WGCNA were used to define bulk transcriptional signatures, which were then integrated with scRNA-seq-derived cell-type marker genes to generate a candidate-gene set with complementary bulk disease-association and cell-type localization evidence. Two-sample Mendelian randomization and colocalization were applied to test whether genetically predicted expression of these candidate genes influences Meniere\u2019s disease risk. Prioritized genes were then mapped to immune-cell subsets, ligand\u2013receptor communication networks, and CD4\n +<\/jats:sup>\n T-cell differentiation trajectories at single-cell resolution, and their expression changes were validated at the mRNA and protein levels in an independent clinical cohort.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Bulk and single-cell analyses yielded 202 Meniere\u2019s disease-associated candidate genes enriched in RNA processing, chromatin regulation, and immune-related pathways. Two-sample Mendelian randomization identified nominal associations between genetically predicted expression of\n SLC39A10, GAB1, and XCL2<\/jats:italic>\n and Meniere\u2019s disease risk. Integration with bulk transcriptomic evidence prioritized increased\n SLC39A10<\/jats:italic>\n expression and reduced\n GAB1<\/jats:italic>\n and\n XCL2<\/jats:italic>\n expression for further analysis. Immune-signature enrichment and single-cell analyses localized their expression-related programs to CD4\n +<\/jats:sup>\n T cells, NK cells, monocytes, B cells, and other peripheral immune populations. CellChat and pseudotime analyses provided complementary descriptions of inferred intercellular communication and CD4\n +<\/jats:sup>\n T-cell state transitions. In an independent clinical cohort,\n SLC39A10, GAB1<\/jats:italic>\n , and\n XCL2<\/jats:italic>\n showed concordant changes at the transcript and protein levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our multi-layered genomic and single-cell analyses prioritize\n SLC39A10<\/jats:italic>\n ,\n GAB1<\/jats:italic>\n , and\n XCL2<\/jats:italic>\n as candidate genes associated with Meniere\u2019s disease and map their expression-related programs to CD4\n +<\/jats:sup>\n T-cell, NK-cell, and other peripheral immune compartments. Together, these findings support a putative zinc transport\u2013immune framework that may contribute to systemic immune dysregulation in Meniere\u2019s disease. This framework should be regarded as a hypothesis generated by integrative genomic and transcriptomic evidence and requires direct validation through measurements of zinc homeostasis, transporter activity, and downstream immune function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2026.1858821","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:23:41Z","timestamp":1788881021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative genomic and single-cell transcriptomic analyses suggest a putative zinc transport\u2013immune axis in Meniere\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanping","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancheng","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]},{"name":"Dongguan Key Laboratory of Environmental Medicine, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuohao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiping","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head & Neck Surgery, The Second People\u2019s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s00415-015-7930-1","article-title":"What is Meni\u00e8re\u2019s disease? 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