{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:05:59Z","timestamp":1789373159927,"version":"build-2803163510"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100011710","name":"Shaanxi Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2024SF-YBXM-037"],"award-info":[{"award-number":["2024SF-YBXM-037"]}],"id":[{"id":"10.13039\/501100011710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","msard-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis and Related Disorders"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.msard.2026.107410","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:14:47Z","timestamp":1785942887000},"page":"107410","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation"],"prefix":"10.1016","volume":"114","author":[{"given":"Yixiang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"She","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikuan","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-7026","authenticated-orcid":false,"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0002","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12967-018-1450-6","article-title":"HLA alleles modulate EBV viral load in multiple sclerosis","volume":"16","author":"Agostini","year":"2018","journal-title":"J. Transl. Med."},{"issue":"23","key":"10.1016\/j.msard.2026.107410_bib0003","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252312906","article-title":"Genes and their impacts on the immune system in the development of multiple sclerosis: a systematic review","volume":"25","author":"Arneth","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"10.1016\/j.msard.2026.107410_bib0004","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.2174\/1570159X22666240124114126","article-title":"Disease modifying strategies in multiple sclerosis: new rays of hope to combat disability?","volume":"22","author":"Bellanca","year":"2024","journal-title":"Curr. Neuropharmacol."},{"issue":"3","key":"10.1016\/j.msard.2026.107410_bib0005","first-page":"160","article-title":"Epstein-Barr virus as a leading cause of multiple sclerosis: mechanisms and implications","volume":"19","author":"Bjornevik","year":"2023","journal-title":"Nat. Rev. Neurol."},{"issue":"7","key":"10.1016\/j.msard.2026.107410_bib0006","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet. Epidemiol."},{"issue":"2","key":"10.1016\/j.msard.2026.107410_bib0007","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/ije\/dyu176","article-title":"EPIC-InterAct Consortium. Network mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways","volume":"44","author":"Burgess","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"10.1016\/j.msard.2026.107410_bib0008","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.3","article-title":"Guidelines for performing mendelian randomization investigations: update for summer 2023","volume":"4","author":"Burgess","year":"2023","journal-title":"Wellcome Open. Res."},{"issue":"3","key":"10.1016\/j.msard.2026.107410_bib0009","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"issue":"11","key":"10.1016\/j.msard.2026.107410_bib0010","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofaa450","article-title":"Genetic determinants of antibody-mediated immune responses to infectious diseases agents: a genome-wide and HLA association study","volume":"7","author":"Butler-Laporte","year":"2020","journal-title":"Open. Forum. Infect. Dis."},{"issue":"3","key":"10.1016\/j.msard.2026.107410_bib0011","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1182\/blood-2007-10-116269","article-title":"Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients","volume":"112","author":"Chaganti","year":"2008","journal-title":"Blood"},{"issue":"7145","key":"10.1016\/j.msard.2026.107410_bib0012","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/447655a","article-title":"Replicating genotype-phenotype associations","volume":"447","author":"Chanock","year":"2007","journal-title":"Nature"},{"issue":"11","key":"10.1016\/j.msard.2026.107410_bib0013","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1016\/j.ajhg.2024.09.001","article-title":"Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies","volume":"111","author":"Chen","year":"2024","journal-title":"Am. J. Hum. Genet."},{"issue":"10","key":"10.1016\/j.msard.2026.107410_bib0014","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41576-022-00493-6","article-title":"Mechanical regulation of chromatin and transcription","volume":"23","author":"Dupont","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.msard.2026.107410_bib0015","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","article-title":"Ion channels in innate and adaptive immunity","volume":"33","author":"Feske","year":"2015","journal-title":"Annu. Rev. Immunol."},{"issue":"4","key":"10.1016\/j.msard.2026.107410_bib0016","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41591-024-02902-1","article-title":"Causal machine learning for predicting treatment outcomes","volume":"30","author":"Feuerriegel","year":"2024","journal-title":"Nat. Med."},{"issue":"5","key":"10.1016\/j.msard.2026.107410_bib0017","doi-asserted-by":"crossref","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."},{"issue":"9","key":"10.1016\/j.msard.2026.107410_bib0018","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/S1474-4422(22)00255-1","article-title":"Genetics of multiple sclerosis: lessons from polygenicity","volume":"21","author":"Goris","year":"2022","journal-title":"Lancet Neurol."},{"issue":"12","key":"10.1016\/j.msard.2026.107410_bib0019","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.amjmed.2020.05.049","article-title":"Treatment of Multiple sclerosis: a review","volume":"133","author":"Hauser","year":"2020","journal-title":"Am. J. Med."},{"key":"10.1016\/j.msard.2026.107410_bib0020","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"issue":"19","key":"10.1016\/j.msard.2026.107410_bib0021","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231911461","article-title":"Whole exome sequencing in multi-incident families identifies novel candidate genes for Multiple sclerosis","volume":"23","author":"Horjus","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"6460","key":"10.1016\/j.msard.2026.107410_bib0022","article-title":"Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility","volume":"365","year":"2019","journal-title":"Science (1979)"},{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0001","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1038\/s41467-019-09773-y","article-title":"International multiple sclerosis genetics consortium. A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis","volume":"10","year":"2019","journal-title":"Nat. Commun."},{"issue":"5","key":"10.1016\/j.msard.2026.107410_bib0023","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002704","article-title":"The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination","volume":"8","author":"Jochum","year":"2012","journal-title":"PLoS. Pathog."},{"issue":"D1","key":"10.1016\/j.msard.2026.107410_bib0024","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: the DrugBank knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic. Acids. Res."},{"issue":"7944","key":"10.1016\/j.msard.2026.107410_bib0025","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"issue":"8","key":"10.1016\/j.msard.2026.107410_bib0026","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat. Med."},{"issue":"11","key":"10.1016\/j.msard.2026.107410_bib0027","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1418","article-title":"Epstein-Barr virus infection, B-cell dysfunction and other risk factors converge in gut-associated lymphoid tissue to drive the immunopathogenesis of multiple sclerosis: a hypothesis","volume":"11","author":"Leffler","year":"2022","journal-title":"Clin. Transl. Immunol."},{"key":"10.1016\/j.msard.2026.107410_bib0028","article-title":"A mendelian randomization study for drug repurposing reveals bezafibrate and fenofibric acid as potential osteoporosis treatments","volume":"14","author":"Li","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"5","key":"10.1016\/j.msard.2026.107410_bib0029","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41423-024-01148-8","article-title":"Cellular metabolism regulates the differentiation and function of T-cell subsets","volume":"21","author":"Ma","year":"2024","journal-title":"Cell Mol. Immunol."},{"issue":"7","key":"10.1016\/j.msard.2026.107410_bib0030","doi-asserted-by":"crossref","DOI":"10.1111\/acel.14171","article-title":"Identification of prospective aging drug targets via mendelian randomization analysis","volume":"23","author":"Mao","year":"2024","journal-title":"Aging Cell"},{"issue":"7","key":"10.1016\/j.msard.2026.107410_bib0031","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.neuron.2021.12.034","article-title":"Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility","volume":"110","author":"Meijer","year":"2022","journal-title":"Neuron"},{"issue":"6","key":"10.1016\/j.msard.2026.107410_bib0032","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/joim.13215","article-title":"Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis","volume":"289","author":"Piehl","year":"2021","journal-title":"J. Intern. Med."},{"key":"10.1016\/j.msard.2026.107410_bib0033","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat. Rev. Methods Primers."},{"issue":"7","key":"10.1016\/j.msard.2026.107410_bib0034","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-011863","article-title":"Therapeutic potential of T-cell receptor targeting the HLA-A*11:01-restricted KRASG12V neoantigen without cross-recognition of the self-antigen RAB7B in solid tumors","volume":"13","author":"Shen","year":"2025","journal-title":"J. ImmunOther Cancer"},{"issue":"16","key":"10.1016\/j.msard.2026.107410_bib0035","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR Statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA, J. Am. Med. Assoc."},{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0036","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41579-022-00770-5","article-title":"Epstein-Barr virus and multiple sclerosis","volume":"21","author":"Soldan","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"issue":"6","key":"10.1016\/j.msard.2026.107410_bib0037","doi-asserted-by":"crossref","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."},{"issue":"16","key":"10.1016\/j.msard.2026.107410_bib0038","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U S. A"},{"issue":"2","key":"10.1016\/j.msard.2026.107410_bib0039","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1084\/jem.20161846","article-title":"Human immunity against EBV-lessons from the clinic","volume":"214","author":"Tangye","year":"2017","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.msard.2026.107410_bib0040","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.43002","article-title":"Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness","volume":"8","author":"Tye","year":"2019","journal-title":"Elife"},{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0041","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1038\/s41467-020-18716-x","article-title":"Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids","volume":"11","author":"van der Graaf","year":"2020","journal-title":"Nat. Commun."},{"issue":"5","key":"10.1016\/j.msard.2026.107410_bib0042","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0043","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12974-017-1049-5","article-title":"Transcriptional profile and Epstein-Barr virus infection status of laser-cut immune infiltrates from the brain of patients with progressive multiple sclerosis","volume":"15","author":"Veroni","year":"2018","journal-title":"J. Neuroinflamm."},{"issue":"7877","key":"10.1016\/j.msard.2026.107410_bib0044","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes","volume":"597","author":"Wang","year":"2021","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.msard.2026.107410_bib0045","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1365-2141.2005.05452.x","article-title":"The immune response to primary EBV infection: a role for natural killer cells","volume":"129","author":"Williams","year":"2005","journal-title":"Br. J. Haematol."},{"issue":"16","key":"10.1016\/j.msard.2026.107410_bib0046","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241612576","article-title":"DNA methylation signatures of multiple sclerosis occur independently of known genetic risk and are primarily attributed to B cells and monocytes","volume":"24","author":"Xavier","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"6589","key":"10.1016\/j.msard.2026.107410_bib0047","article-title":"Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease","volume":"376","author":"Yazar","year":"2022","journal-title":"Science (1979)"},{"issue":"1","key":"10.1016\/j.msard.2026.107410_bib0048","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12943-022-01616-7","article-title":"Wnt signaling in colorectal cancer: pathogenic role and therapeutic target","volume":"21","author":"Zhao","year":"2022","journal-title":"Mol. Cancer"}],"container-title":["Multiple Sclerosis and Related Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211034826004451?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211034826004451?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:06:10Z","timestamp":1789369570000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211034826004451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":48,"alternative-id":["S2211034826004451"],"URL":"https:\/\/doi.org\/10.1016\/j.msard.2026.107410","relation":{},"ISSN":["2211-0348"],"issn-type":[{"value":"2211-0348","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation","name":"articletitle","label":"Article Title"},{"value":"Multiple Sclerosis and Related Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.msard.2026.107410","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"107410"}}