{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:18:28Z","timestamp":1792700308014,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":1208,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM138597"],"award-info":[{"award-number":["R01GM138597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL127564"],"award-info":[{"award-number":["R01HL127564"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL142711"],"award-info":[{"award-number":["R01HL142711"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM138597"],"award-info":[{"award-number":["R01GM138597"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL127564"],"award-info":[{"award-number":["R01HL127564"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL142711"],"award-info":[{"award-number":["R01HL142711"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post\u2013COVID-19 pneumonia were performed in MVP subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases\u2009=\u20094,325; Ncontrols\u2009=\u2009507,640; OR\u2009=\u20090.89 [0.82\u20130.97]; P\u2009=\u20096.86\u2009\u00d7\u200910\u22123) and joint meta-analyses with the HGI (Ncases\u2009=\u200913,320; Ncontrols\u2009=\u20091,508,841; OR, 0.90 [0.86\u20130.95]; P\u2009=\u20098.99\u2009\u00d7\u200910\u22125). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases\u2009=\u200919,168\/Ncontrols\u2009=\u2009492,854; OR, 0.98 [0.95\u20131.01]; P\u2009=\u20090.06) but was nominally significant (P\u2009&amp;lt;\u20090.05) in the joint meta-analysis with the HGI (Ncases\u2009=\u200944,820; Ncontrols\u2009=\u20091,775,827; OR, 0.97 [0.95\u20131.00]; P\u2009=\u20090.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post\u2013COVID-19 pneumonia events (OR, 0.82 [0.72\u20130.93]; P\u2009=\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202109-2166oc","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T11:26:10Z","timestamp":1656588370000},"page":"1220-1229","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":44,"title":["A\n                    <i>MUC5B<\/i>\n                    Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality"],"prefix":"10.1093","volume":"206","author":[{"given":"Anurag","family":"Verma","sequence":"first","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania"},{"name":"Department of Medicine, Perelman School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Minnier","sequence":"additional","affiliation":[{"name":"OHSU-PSU School of Public Health and"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon"},{"name":"VA Portland Health Care System, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily S.","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pulmonary, Critical Care, Sleep, and Allergy Section"},{"name":"Channing Division of Network Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Huffman","sequence":"additional","affiliation":[{"name":"MAVERIC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Gao","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon"},{"name":"VA Portland Health Care System, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Medicine, Cardiovascular, Brigham & Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk-Lam","family":"Ho","sequence":"additional","affiliation":[{"name":"MAVERIC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chih","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Providence VA Healthcare System, Providence, Rhode Island"},{"name":"Alpert Medical School & School of Public Health, Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Cho","sequence":"additional","affiliation":[{"name":"MAVERIC"},{"name":"Medicine, Aging, Brigham & Women\u2019s Hospital and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan R.","family":"Gorman","sequence":"additional","affiliation":[{"name":"MAVERIC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nallakkandi","family":"Rajeevan","sequence":"additional","affiliation":[{"name":"Yale Center for Medical Informatics"},{"name":"Clinical Epidemiology Research Center (CERC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiju","family":"Pyarajan","sequence":"additional","affiliation":[{"name":"MAVERIC"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Garcon","sequence":"additional","affiliation":[{"name":"MAVERIC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Meigs","sequence":"additional","affiliation":[{"name":"Medicine, General Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan V.","family":"Sun","sequence":"additional","affiliation":[{"name":"Epidemiology, School of Public Health and"},{"name":"Atlanta VA Healthcare System, Decatur, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Reaven","sequence":"additional","affiliation":[{"name":"Department of Medicine, Phoenix VA Healthcare System, Phoenix, Arizona"},{"name":"College of Medicine, University of Arizona, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"McGeary","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Providence VA Medical Center, Providence, Rhode Island"},{"name":"Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medicine, Gastroenterology, Durham VA Medical Center, Durham, North Carolina"},{"name":"Department of Medicine, Gastroenterology, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry, and"},{"name":"VA Connecticut Healthcare System, West Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Lynch","sequence":"additional","affiliation":[{"name":"VA Informatics & Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, Utah"},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Corporal Michael J. 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