{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:49:46Z","timestamp":1790624986036,"version":"4.1.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"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>Previous studies have found that the persistence of herpesvirus significantly increases the risk of idiopathic pulmonary fibrosis (IPF), but it is unclear whether this effect is causal. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between three herpesvirus infections and IPF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We used genome-wide association studies (GWAS) data from three independent datasets, including FinnGen cohort, Milieu Int\u00e9rieur cohort, and 23andMe cohort, to screen for instrumental variables (IVs) of herpesvirus infection or herpesvirus-related immunoglobulin G (IgG) levels. Outcome dataset came from the largest meta-analysis of IPF susceptibility currently available.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In the FinnGen cohort, genetically predicted Epstein-Barr virus (EBV) (OR = 1.105, 95%CI: 0.897\u20131.149, p = 0.815), cytomegalovirus (CMV) (OR = 1.073, 95%CI: 0.926\u20131.244, p = 0.302) and herpes simplex (HSV) infection (OR = 0.906, 95%CI: 0.753\u20131.097, p = 0.298) were not associated with the risk of IPF. In the Milieu Int\u00e9rieur cohort, we found no correlations between herpesvirus-related IgG EBV nuclear antigen-1 (EBNA1) (OR = 0.968, 95%CI: 0.782\u20131.198, p = 0.764), EBV viral capsid antigen (VCA) (OR = 1.061, 95CI%: 0.811\u20131.387, p = 0.665), CMV (OR = 1.108, 95CI%: 0.944\u20131.314, p = 0.240), HSV-1 (OR = 1.154, 95%CI: 0.684\u20131.945, p = 0.592) and HSV-2 (OR = 0.915, 95%CI: 0.793\u20131.056, p = 0.225) and IPF risk. Moreover, in the 23andMe cohort, no evidence of associations between mononucleosis (OR = 1.042, 95%CI: 0.709\u20131.532, p = 0.832) and cold scores (OR = 0.906, 95%CI: 0.603\u20131.362, p = 0.635) and IPF were found. Sensitivity analysis confirmed the robustness of our results.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study provides preliminary evidence that EBV, CMV, and HSV herpesviruses, and herpesviruses-related IgG levels, are not causally linked to IPF. Further MR analysis will be necessary when stronger instrument variables and GWAS with larger sample sizes become available.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0295082","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T18:52:24Z","timestamp":1701197544000},"page":"e0295082","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mendelian randomization reveals no correlations between herpesvirus infection and idiopathic pulmonary fibrosis"],"prefix":"10.1371","volume":"18","author":[{"given":"Haihao","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-1753","authenticated-orcid":true,"given":"Ganzhu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"pone.0295082.ref001","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/S0140-6736(17)30866-8","article-title":"Idiopathic pulmonary fibrosis","volume":"389","author":"L. 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