{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T23:16:59Z","timestamp":1788045419921,"version":"build-2784847793"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62531007"],"award-info":[{"award-number":["62531007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62222104"],"award-info":[{"award-number":["62222104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62172130"],"award-info":[{"award-number":["62172130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heilongjiang Postdoctoral Fund","award":["LBH-Q20030"],"award-info":[{"award-number":["LBH-Q20030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genome-wide association study\u00a0analysis has revealed the significant influence of genetic factors in the progression of COVID-19. However, the impact of these genetic variants on gene expression in various cell types remains largely unexplored. Here, we profiled immune cells from 42 COVID-19 cases (involving five\u00a0stages) and 11 healthy individuals, and performed a single-cell RNA-seq assay with &amp;gt;200\u00a0000 cells to investigate cell\u00a0type-specific and stage-specific genetic effects of genetic variants. Single-cell expression quantitative trait loci\u00a0analysis of eight\u00a0distinct cell types showed that the expression of 2593 genes is significantly associated with common genetic polymorphisms, and that the majority of these genes show their most prominent effects in specific cell types. Furthermore, we also discovered new gene associations for COVID-19-risk variants identified from genome-wide association studies and highlighted the monocytes in which their effects are most prominent. We found that 57 genes were regulated by variants associated with COVID-19, with significant enrichment for dynamic effects. In summary, our results highlight the importance of studying context-specific genetic regulation of gene expression\u00a0and provide insights into the mechanisms underlying genetic susceptibility to COVID-19.<\/jats:p>","DOI":"10.1093\/nargab\/lqaf130","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:24:37Z","timestamp":1759832677000},"source":"Crossref","is-referenced-by-count":1,"title":["Cell type-specific eQTL analysis of COVID-19 based on single-cell transcriptomic data"],"prefix":"10.1093","volume":"7","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyu","family":"Du","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanzhi","family":"He","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senwei","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duoyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The 2nd Affiliated Hospital of Harbin Medical University, Harbin Medical University , Heilongjiang,\u00a0Harbin 150081,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqiao","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Harbin Medical University , Heilongjiang, Harbin 150081,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6665-6710","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , Heilongjiang,\u00a0Harbin\u00a0 150081 ,\u00a0","place":["China"]},{"name":"NHC Key Laboratory of Molecular Probe and Targeted Diagnosis and Therapy, Harbin Medical University , Heilongjiang,\u00a0Harbin 150028,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"2025100706243423600_B1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2025100706243423600_B2","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.immuni.2020.05.002","article-title":"Immunology of COVID-19: current state of the science","volume":"52","author":"Vabret","year":"2020","journal-title":"Immunity"},{"key":"2025100706243423600_B3","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(21)02796-3","article-title":"Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020\u201321","volume":"399","author":"Collaborators","year":"2022","journal-title":"Lancet"},{"key":"2025100706243423600_B4","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41586-023-06034-3","article-title":"GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19","volume":"617","author":"Pairo-Castineira","year":"2023","journal-title":"Nature"},{"key":"2025100706243423600_B5","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41586-022-04447-0","article-title":"Human genetic and immunological determinants of critical COVID-19 pneumonia","volume":"603","author":"Zhang","year":"2022","journal-title":"Nature"},{"key":"2025100706243423600_B6","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41588-021-00854-7","article-title":"Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity","volume":"53","author":"Shelton","year":"2021","journal-title":"Nat Genet"},{"key":"2025100706243423600_B7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.cell.2020.12.006","article-title":"Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks","volume":"184","author":"Schneider","year":"2021","journal-title":"Cell"},{"key":"2025100706243423600_B8","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.jinf.2023.01.025","article-title":"IL1RA mediated the effects of aspirin on COVID-19 severity: a Mendelian randomization study","volume":"86","author":"Liu","year":"2023","journal-title":"J Infect"},{"key":"2025100706243423600_B9","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1093\/bfgp\/elac033","article-title":"Genome-wide Mendelian randomization and single-cell RNA sequencing analyses identify the causal effects of COVID-19 on 41 cytokines","volume":"21","author":"Wang","year":"2022","journal-title":"Brief Funct Genomics"},{"key":"2025100706243423600_B10","doi-asserted-by":"publisher","first-page":"eabf3041","DOI":"10.1126\/science.abf3041","article-title":"Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease","volume":"376","author":"Yazar","year":"2022","journal-title":"Science"},{"key":"2025100706243423600_B11","doi-asserted-by":"publisher","first-page":"eabf1970","DOI":"10.1126\/science.abf1970","article-title":"Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus","volume":"376","author":"Perez","year":"2022","journal-title":"Science"},{"key":"2025100706243423600_B12","doi-asserted-by":"publisher","first-page":"199341","DOI":"10.1016\/j.virusres.2024.199341","article-title":"Exploring COVID-19 causal genes through disease-specificcis-eQTLs","volume":"342","author":"Zhang","year":"2024","journal-title":"Virus Res"},{"key":"2025100706243423600_B13","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.immuni.2021.05.006","article-title":"SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2","volume":"54","author":"Lu","year":"2021","journal-title":"Immunity"},{"key":"2025100706243423600_B14","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/s41591-020-0944-y","article-title":"A single-cell atlas of the peripheral immune response in patients with severe COVID-19","volume":"26","author":"Wilk","year":"2020","journal-title":"Nat Med"},{"key":"2025100706243423600_B15","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.imlet.2022.08.006","article-title":"Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations","volume":"249","author":"Ma","year":"2022","journal-title":"Immunol Lett"},{"key":"2025100706243423600_B16","doi-asserted-by":"publisher","first-page":"e0247128","DOI":"10.1371\/journal.pone.0247128","article-title":"Transcriptomic profiling and genomic mutational analysis of human coronavirus (HCoV)-229E -infected human cells","volume":"16","author":"Friedman","year":"2021","journal-title":"PLoS One"},{"key":"2025100706243423600_B17","doi-asserted-by":"publisher","article-title":"SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1alpha\/XBP1 ER stress pathway in human lung-derived cells","author":"Nguyen","DOI":"10.1101\/2021.12.30.474519"},{"key":"2025100706243423600_B18","doi-asserted-by":"publisher","first-page":"1029093","DOI":"10.3389\/fphar.2022.1029093","article-title":"Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex","volume":"13","author":"Feng","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025100706243423600_B19","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2025100706243423600_B20","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat Methods"},{"key":"2025100706243423600_B21","doi-asserted-by":"publisher","first-page":"e67899","DOI":"10.1371\/journal.pone.0067899","article-title":"An information-theoretic machine learning approach to expression QTL analysis","volume":"8","author":"Huang","year":"2013","journal-title":"PLoS One"},{"key":"2025100706243423600_B22","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","journal-title":"PLoS Genet"},{"key":"2025100706243423600_B23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/ng.3506","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","journal-title":"Nat Genet"},{"key":"2025100706243423600_B24","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41586-022-04702-4","article-title":"FcgammaR-mediated SARS-CoV-2 infection of monocytes activates inflammation","volume":"606","author":"Junqueira","year":"2022","journal-title":"Nature"},{"key":"2025100706243423600_B25","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell\u2013cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"2025100706243423600_B26","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/qjmed\/hcac234","article-title":"MIF is a common genetic determinant of COVID-19 symptomatic infection and severity","volume":"116","author":"Shin","year":"2023","journal-title":"QJM"},{"key":"2025100706243423600_B27","doi-asserted-by":"publisher","first-page":"1236374","DOI":"10.3389\/fimmu.2023.1236374","article-title":"Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients","volume":"14","author":"Westmeier","year":"2023","journal-title":"Front Immunol"},{"key":"2025100706243423600_B28","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Consortium","year":"2020","journal-title":"Science"},{"key":"2025100706243423600_B29","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13059-021-02293-3","article-title":"Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells","volume":"22","author":"Neavin","year":"2021","journal-title":"Genome Biol"},{"key":"2025100706243423600_B30","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41588-022-01066-3","article-title":"Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation","volume":"54","author":"Soskic","year":"2022","journal-title":"Nat Genet"},{"key":"2025100706243423600_B31","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cytogfr.2021.10.004","article-title":"S100A8\/A9 in COVID-19 pathogenesis: impact on clinical outcomes","volume":"63","author":"Mellett","year":"2022","journal-title":"Cytokine Growth Factor Rev"},{"key":"2025100706243423600_B32","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"The Lancet"},{"key":"2025100706243423600_B33","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2020.06.017","article-title":"Cytokine Storms: understanding COVID-19","volume":"53","author":"Mangalmurti","year":"2020","journal-title":"Immunity"},{"key":"2025100706243423600_B34","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1016\/j.cell.2020.08.001","article-title":"Severe COVID-19 is marked by a dysregulated myeloid cell compartment","volume":"182","author":"Schulte-Schrepping","year":"2020","journal-title":"Cell"},{"key":"2025100706243423600_B35","doi-asserted-by":"publisher","first-page":"1246949","DOI":"10.1126\/science.1246949","article-title":"Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression","volume":"343","author":"Fairfax","year":"2014","journal-title":"Science"},{"key":"2025100706243423600_B36","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41588-018-0046-7","article-title":"Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response","volume":"50","author":"Alasoo","year":"2018","journal-title":"Nat Genet"},{"key":"2025100706243423600_B37","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.ajhg.2023.02.008","article-title":"Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease","volume":"110","author":"Hamilton","year":"2023","journal-title":"Am Hum Genet"},{"key":"2025100706243423600_B38","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1136\/ard-2022-222852","article-title":"EULAR study group on \u2018MHC-I-opathy\u2019: identifying disease-overarching mechanisms across disciplines and borders","volume":"82","author":"Kuiper","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"2025100706243423600_B39","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41586-022-04632-1","article-title":"Programme of self-reactive innate-like T cell-mediated cancer immunity","volume":"605","author":"Chou","year":"2022","journal-title":"Nature"},{"key":"2025100706243423600_B40","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3389\/fphar.2016.00353","article-title":"FCERI and histamine metabolism gene variability in selective responders to NSAIDS","volume":"7","author":"Amo","year":"2016","journal-title":"Front Pharmacol"},{"key":"2025100706243423600_B41","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1111\/j.1398-9995.2011.02681.x","article-title":"Gene\u2013vitamin D interactions on food sensitization: a prospective birth cohort study","volume":"66","author":"Liu","year":"2011","journal-title":"Allergy"},{"key":"2025100706243423600_B42","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41591-021-01310-z","article-title":"Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19","volume":"27","author":"Gaziano","year":"2021","journal-title":"Nat Med"},{"key":"2025100706243423600_B43","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025100706243423600_B44","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1038\/ng.479","article-title":"Genetic variants at CD28, PRDM1 and CD2\/CD58 are associated with rheumatoid arthritis risk","volume":"41","author":"Raychaudhuri","year":"2009","journal-title":"Nat Genet"},{"key":"2025100706243423600_B45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev-med-042220-012417","article-title":"COVID-19: inflammatory profile","volume":"73","author":"Wang","year":"2022","journal-title":"Annu Rev Med"},{"key":"2025100706243423600_B46","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/s41586-020-2818-3","article-title":"The major genetic risk factor for severe COVID-19 is inherited from Neanderthals","volume":"587","author":"Zeberg","year":"2020","journal-title":"Nature"}],"container-title":["NAR Genomics and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/7\/4\/lqaf130\/64528421\/lqaf130.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/7\/4\/lqaf130\/64528421\/lqaf130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:24:37Z","timestamp":1759832677000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nargab\/article\/doi\/10.1093\/nargab\/lqaf130\/8276624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10,7]]}},"URL":"https:\/\/doi.org\/10.1093\/nargab\/lqaf130","relation":{},"ISSN":["2631-9268"],"issn-type":[{"value":"2631-9268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,10,7]]},"article-number":"lqaf130"}}