{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:31:05Z","timestamp":1790299865066,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI070503"],"award-info":[{"award-number":["U19 AI070503"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000427"],"award-info":[{"award-number":["UL1TR000427"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL070831"],"award-info":[{"award-number":["P01 HL070831"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32 HL095268"],"award-info":[{"award-number":["F32 HL095268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL007605"],"award-info":[{"award-number":["T32 HL007605"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to identify variation in genes with known antiviral and pro\u2010inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus\u2010induced exacerbations during the peak fall season.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The associations between genetic variation at 326 <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (<jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content>). Significant associations in RhinoGen were further validated using virus\u2010induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (<jats:styled-content style=\"fixed-case\">COAST<\/jats:styled-content>) birth cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant excess of <jats:italic>P<\/jats:italic> values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small <jats:italic>P<\/jats:italic> values. Six of those genes (<jats:italic><jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>4<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">MX<\/jats:styled-content>1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">VDR<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">DDX<\/jats:styled-content>58,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">EIF<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>2<\/jats:italic>) also showed significant associations with asthma exacerbations in the <jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content> study or with asthma or virus\u2010induced wheezing phenotypes in the <jats:styled-content style=\"fixed-case\">COAST<\/jats:styled-content> study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus\u2010induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus\u2010induced exacerbations of asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12642","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T05:36:48Z","timestamp":1443073008000},"page":"112-124","source":"Crossref","is-referenced-by-count":45,"title":["Genetic associations with viral respiratory illnesses and asthma control in\u00a0children"],"prefix":"10.1111","volume":"46","author":[{"given":"D. A.","family":"Loisel","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago IL USA"},{"name":"Department of Biology Saint Michael's College Colchester VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. S.","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Ledreborg All\u00e9 34 DK\u20102820 Copenhagen Denmark"},{"name":"Steno Diabetes Center Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. J.","family":"Tisler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. D.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E.","family":"Gangnon","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin School of Medicine and Public Health Madison WI USA"},{"name":"Department of Population Health Sciences University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kreiner\u2010M\u00f8ller","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Ledreborg All\u00e9 34 DK\u20102820 Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"B\u00f8nnelykke","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Ledreborg All\u00e9 34 DK\u20102820 Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Ledreborg All\u00e9 34 DK\u20102820 Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"R. F.","family":"Lemanske","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison WI USA"},{"name":"Department of Medicine University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. L.","family":"Nicolae","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago IL USA"},{"name":"Department of Medicine University of Chicago Chicago IL USA"},{"name":"Department of Statistics University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. E.","family":"Gern","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ober","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,23]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"543","article-title":"Risk of primary infection and reinfection with respiratory syncytial virus","volume":"140","author":"Glezen WP","year":"1986","journal-title":"Am J Dis Child"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.15.1440"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e3283352f7c"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01031.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200802-309OC"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.33"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.06.037"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.162"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.310.6989.1225"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200312-1647OC"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211592"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0055OC"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901386"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001178"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.07.029"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.12.582"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.01.059"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/375069"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/136.1.109"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02501-06"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000966"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.109"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2830"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12213"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3038.13.s.15.8.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.06.016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137323.112"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr917"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2007.04.006"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-005-0232-1"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.10.006"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/382171a0"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/382174a0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.10.002"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.6.2003019"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246949"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00024-13"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-239855"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2010.12.004"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.09.53"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-009-0643-8"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2012.11.005"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200404-447OC"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200403-412OC"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-71"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.2310\/JIM.0b013e318220df41"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1086\/527488"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.22179"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-12-103"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2004.05.014"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh169"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09906"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903291"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007582"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024395"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.12642","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.12642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:03:11Z","timestamp":1696298591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.12642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,23]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/cea.12642"],"URL":"https:\/\/doi.org\/10.1111\/cea.12642","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,23]]}}}