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We utilized differential gene expression analysis and performed weighted gene coexpression network analysis on 25\u00a0060 genes, to identify gene transcripts and network modules associated with total IgE, adjusting for age and gender. We used pathway enrichment analyses to identify key biological pathways underlying significant modules. We compared findings that replicated between both populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 31 transcripts associated with total IgE that replicated between the two study cohorts. These results were notable for increased eosinophil\u2010related transcripts (including<jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">CLC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">SMPD<\/jats:styled-content>3,<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>23 and<jats:styled-content style=\"fixed-case\">CEBPE<\/jats:styled-content><\/jats:italic>). Pathway enrichment identified the regulation of T cell tolerance as important in the determination of total IgE levels, supporting a key role for<jats:italic><jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content>1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>These results provide robust evidence that biologically meaningful gene expression profiles (relating to eosinophilic and regulatory T cell pathways in particular) associated with total IgE levels can be identified in individuals diagnosed with asthma during childhood. These profiles and their constituent genes may represent novel therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13249","type":"journal-article","created":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T22:04:55Z","timestamp":1534284295000},"page":"1654-1664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Novel eosinophilic gene expression networks associated with IgE in two distinct asthma populations"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-7215","authenticated-orcid":false,"given":"Yamini V.","family":"Virkud","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology Department of Pediatrics Harvard Medical School Massachusetts General Hospital for Children Boston Massachusetts"},{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-1822","authenticated-orcid":false,"given":"Rachel S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien C.","family":"Croteau\u2010Chonka","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6139-5320","authenticated-orcid":false,"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Allergy and Immunology Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Dahlin","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiana","family":"Avila","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Nacional de Ni\u00f1os San Jose Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Raby","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Lasky\u2010Su","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Harvard Medical School Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2004.00526.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01621.x"},{"key":"e_1_2_8_4_1","unstructured":"U.S. Department of Health and Human Services National Institutes of Health.Global Initiative for Asthma Management and Prevention. 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