{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:22Z","timestamp":1790402482893,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874466, 81904176"],"award-info":[{"award-number":["81874466, 81904176"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2021JJ30531"],"award-info":[{"award-number":["2021JJ30531"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014472","name":"Scientific Research Foundation of Hunan Provincial Education Department","doi-asserted-by":"publisher","award":["21B0389"],"award-info":[{"award-number":["21B0389"]}],"id":[{"id":"10.13039\/100014472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Previous observational or retrospective studies have suggested an association between inflammatory bowel disease (IBD) and herpes virus infections. Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between IBD and herpes virus infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In genome-wide association study (GWAS) datasets of the International Inflammatory Bowel Disease Genetics Consortium, we obtained genetic instrumental variables for three phenotypes from 34,652 participants (12,882 IBD cases and 21,770 controls), 27,432 participants [6,968 ulcerative colitis (UC) cases and 20,464 controls], and 20,883 participants [5,956 Crohn\u2019s disease (CD) cases and 14,927 controls], respectively. Summary statistics for herpes virus infections (chickenpox, herpes zoster, and mononucleosis) were obtained from the FinnGen database. MR results were expressed as odds ratio (OR) with 95% confidence interval (CI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study found no evidence of a causal effect of genetically predicted IBD on herpes virus infections [<jats:italic>P<\/jats:italic> value for inverse variance weighting (IVW): 0.063 to 0.652]. For the subtypes of IBD, UC had a suggestive association with mononucleosis (<jats:italic>P<\/jats:italic> value for IVW: 0.023). It appeared that CD was also weakly associated with mononucleosis (<jats:italic>P<\/jats:italic> value for IVW: 0.058; <jats:italic>P<\/jats:italic> value for Weighted median: 0.036). In addition, we found a suggestive causality for CD on chickenpox (<jats:italic>P<\/jats:italic> value for IVW: 0.038). Neither UC (<jats:italic>P<\/jats:italic> value for IVW: 0.574) nor CD (<jats:italic>P<\/jats:italic> value for IVW: 0.168) has a causal effect on herpes zoster. The results of the bidirectional MR analysis did not indicate that herpes virus infections were associated with IBD, UC or CD (<jats:italic>P<\/jats:italic> value for IVW: 0.239 to 0.888).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study showed a suggestive causality for both CD-chickenpox and UC-mononucleosis, despite no associations reaching a statistical significance value after corrections for multiple testing. There was no evidence of a causal association between IBD and its two subtypes on herpes zoster.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1203707","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T07:41:57Z","timestamp":1688370117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Causal association between inflammatory bowel disease and herpes virus infections: a two-sample bidirectional Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Menglong","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/540S97a","article-title":"Inflammatory bowel disease","volume":"540","author":"Hodson","year":"2016","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet (London England)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cell.2020.03.007","article-title":"Challenges, progress, and prospects of developing therapies to treat autoimmune diseases","volume":"181","author":"Fugger","year":"2020","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.186","article-title":"Heat waves, incidence of infectious gastroenteritis, and relapse rates of inflammatory bowel disease: a retrospective controlled observational study","volume":"108","author":"Manser","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/mib.0000000000000735","article-title":"Association between parkinson\u2019s disease and inflammatory bowel disease: a nationwide Taiwanese retrospective cohort study","volume":"22","author":"Lin","year":"2016","journal-title":"Inflamm Bowel Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.63","article-title":"Inflammatory bowel disease is associated with an increased incidence of cardiovascular events","volume":"106","author":"Yarur","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells10082122","article-title":"Innate immune responses to herpesvirus infection","volume":"10","author":"O\u2019Connor","year":"2021","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.22950","article-title":"Varicella zoster virus infection in inflammatory bowel disease","volume":"18","author":"Cullen","year":"2012","journal-title":"Inflamm Bowel Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3904\/kjim.2020.386","article-title":"Seroprevalence of viral infectious diseases and associated factors in Korean patients with inflammatory bowel diseases","volume":"37","author":"Hong","year":"2022","journal-title":"Korean J Internal Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy311","article-title":"Herpes zoster incidence in inflammatory bowel disease patients: a population-based study","volume":"25","author":"C\u00f4t\u00e9-Daigneault","year":"2019","journal-title":"Inflamm Bowel Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000026863","article-title":"The incidence rate of herpes zoster in inflammatory bowel disease: a meta-analysis of cohort studies","volume":"100","author":"Lai","year":"2021","journal-title":"Medicine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.915453","article-title":"Epstein-Barr Virus and human cytomegalovirus infection in intestinal mucosa of Chinese patients with inflammatory bowel disease","volume":"13","author":"Wang","year":"2022","journal-title":"Front Microbiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.2","article-title":"Guidelines for performing mendelian randomization investigations","volume":"4","author":"Burgess","year":"2019","journal-title":"Wellcome Open Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","article-title":"Mendelian randomization: prospects, potentials, and limitations","volume":"33","author":"Smith","year":"2004","journal-title":"Int J Epidemiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.12.072","article-title":"Hospitalization for varicella and zoster in children with inflammatory bowel disease","volume":"171","author":"Adams","year":"2016","journal-title":"J Pediatr"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","article-title":"Reading mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ (Clinical Res ed)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat Genet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1101\/2022.03.03.22271360","article-title":"Finngen: unique genetic insights from combining isolated population and national health register data","author":"Mitja","year":"2022","journal-title":"medRxiv"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"Abecasis","year":"2010","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1080982","article-title":"Constipation and cardiovascular disease: a two-sample mendelian randomization analysis","volume":"10","author":"Dong","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210394459","article-title":"Using multiple genetic variants as instrumental variables for modifiable risk factors","volume":"21","author":"Palmer","year":"2012","journal-title":"Stat Methods Med Res"},{"key":"B23","doi-asserted-by":"publisher","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"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz469","article-title":"Phenoscanner V2: an expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinf (Oxford England)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1038\/s41467-019-09572-5","article-title":"Genome-wide association study of medication-use and associated disease in the uk biobank","volume":"10","author":"Wu","year":"2019","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac085","article-title":"Immunosuppressants contribute to a reduced risk of parkinson\u2019s disease in rheumatoid arthritis","volume":"51","author":"Guo","year":"2022","journal-title":"Int J Epidemiol"},{"key":"B27","doi-asserted-by":"publisher","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"},{"key":"B28","doi-asserted-by":"publisher","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"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7221","article-title":"A framework for the investigation of pleiotropy in two-sample summary data mendelian randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ (Clinical Res ed)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using gwas summary data","volume":"13","author":"Hemani","year":"2017","journal-title":"PloS Genet"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-019-03706-9","article-title":"Increased risk of herpes zoster infection in patients with inflammatory bowel disease: a meta-analysis of cohort studies","volume":"39","author":"Ning","year":"2020","journal-title":"Eur J Clin Microbiol Infect Diseases: Off Publ Eur Soc Clin Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12182","article-title":"Increased risk of herpes zoster among 108 604 patients with inflammatory bowel disease","volume":"37","author":"Long","year":"2013","journal-title":"Alimentary Pharmacol Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2009.06140.x","article-title":"Population-based cases control study of inflammatory bowel disease risk factors","volume":"25","author":"Gearry","year":"2010","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20110","article-title":"Genome-wide gene expression differences in crohn\u2019s disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis","volume":"13","author":"Wu","year":"2007","journal-title":"Inflamm Bowel Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"Podolsky","year":"2002","journal-title":"New Engl J Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory bowel disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu Rev Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1203707\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T07:42:02Z","timestamp":1688370122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1203707\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,3]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2023.1203707"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1203707","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,3]]},"article-number":"1203707"}}