{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:12:23Z","timestamp":1788293543859,"version":"build-2803163510"},"reference-count":45,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["MD011764"],"award-info":[{"award-number":["MD011764"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL079966"],"award-info":[{"award-number":["HL079966"]}],"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":["HL117191"],"award-info":[{"award-number":["HL117191"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2020,9,30]]},"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial\/ethnic groups.<\/jats:p><jats:p>To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.<\/jats:p><jats:p>In the meta-analysis of GWAS, an SNP in<jats:italic>FLJ22447<\/jats:italic>(rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34\u20131.79, p=6.3\u00d710<jats:sup>\u22129<\/jats:sup>). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the<jats:italic>FLJ22447<\/jats:italic>locus, which was in turn associated with increased expression of<jats:italic>KCNJ2-AS1<\/jats:italic>in nasal airway epithelium from Puerto Rican children and adolescents (\u03b2=0.10, p=2.18\u00d710<jats:sup>\u22127<\/jats:sup>).<\/jats:p><jats:p>SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in<jats:italic>FLJ22447<\/jats:italic>and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (<jats:italic>KCNJ2-AS1<\/jats:italic>).<\/jats:p>","DOI":"10.1183\/13993003.02693-2020","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T20:10:29Z","timestamp":1603397429000},"page":"2002693","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["A genome-wide association study of severe asthma exacerbations in Latino children and adolescents"],"prefix":"10.1183","volume":"57","author":[{"given":"Qi","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-9885","authenticated-orcid":false,"given":"Erick","family":"Forno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Herrera-Luis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-437X","authenticated-orcid":false,"given":"Maria","family":"Pino-Yanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cancan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-0453","authenticated-orcid":false,"given":"Raimon","family":"Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-3077","authenticated-orcid":false,"given":"Yueh-Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Acosta-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-001X","authenticated-orcid":false,"given":"Donglei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Huntsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiana","family":"Avila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Boutaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Cloutier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel E.","family":"Soto-Quiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-4672","authenticated-orcid":false,"given":"Cheng-Jian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7196-303X","authenticated-orcid":false,"given":"Scott T.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lasky-Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan R.","family":"Kiedrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Bomberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio L.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glorisa","family":"Canino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7196-8703","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8567-3252","authenticated-orcid":false,"given":"Gerard H.","family":"Koppelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban G.","family":"Burchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"2024102102034453000_57.4.2002693.1","unstructured":"Center for Disease Control and Prevention . Asthma. Data, statistics and surveillance. www.cdc.gov\/asthma\/most_recent_data.htm. Date last accessed: September 18, 2020."},{"key":"2024102102034453000_57.4.2002693.2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201703-259OC"},{"key":"2024102102034453000_57.4.2002693.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.12.983"},{"key":"2024102102034453000_57.4.2002693.4","first-page":"1","article-title":"Asthma prevalence, health care use, and mortality: United States, 2005\u20132009","volume":"32","author":"Akinbami","year":"2011","journal-title":"Natl Health Stat Report"},{"key":"2024102102034453000_57.4.2002693.5","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1164\/rccm.201606-1213PP","article-title":"Predicting severe asthma exacerbations in children","volume":"195","author":"Puranik","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102102034453000_57.4.2002693.6","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01505-2016"},{"key":"2024102102034453000_57.4.2002693.7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41588-017-0014-7","article-title":"Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks","volume":"50","author":"Demenais","year":"2018","journal-title":"Nat Genet"},{"key":"2024102102034453000_57.4.2002693.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.888"},{"key":"2024102102034453000_57.4.2002693.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2830"},{"key":"2024102102034453000_57.4.2002693.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.04.039"},{"key":"2024102102034453000_57.4.2002693.11","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.73"},{"key":"2024102102034453000_57.4.2002693.12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201401-0186PP"},{"key":"2024102102034453000_57.4.2002693.13","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-207199"},{"key":"2024102102034453000_57.4.2002693.14","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1164\/rccm.201707-1493OC","article-title":"A Genome-wide association study in Hispanics\/latinos identifies novel signals for lung function. The Hispanic Community Health Study\/Study of Latinos","volume":"198","author":"Burkart","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102102034453000_57.4.2002693.15","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201712-2529OC"},{"key":"2024102102034453000_57.4.2002693.16","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"2024102102034453000_57.4.2002693.17","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0264OC"},{"key":"2024102102034453000_57.4.2002693.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.04.032"},{"key":"2024102102034453000_57.4.2002693.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.12.609"},{"key":"2024102102034453000_57.4.2002693.20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2466-6-15"},{"key":"2024102102034453000_57.4.2002693.21","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/S2213-2600(18)30466-1","article-title":"DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study","volume":"7","author":"Forno","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2024102102034453000_57.4.2002693.22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"2024102102034453000_57.4.2002693.23","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3038.13.s.15.1.x"},{"key":"2024102102034453000_57.4.2002693.24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2001.01072.x"},{"key":"2024102102034453000_57.4.2002693.25","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.jaci.2019.12.911","article-title":"Nasal DNA methylation profiling of asthma and rhinitis","volume":"145","author":"Qi","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2024102102034453000_57.4.2002693.26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"2024102102034453000_57.4.2002693.27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"2024102102034453000_57.4.2002693.28","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"2024102102034453000_57.4.2002693.29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1179"},{"key":"2024102102034453000_57.4.2002693.30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1070"},{"key":"2024102102034453000_57.4.2002693.31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.1.29"},{"key":"2024102102034453000_57.4.2002693.32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1351"},{"key":"2024102102034453000_57.4.2002693.33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1018"},{"key":"2024102102034453000_57.4.2002693.34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41588-018-0121-0","article-title":"A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases","volume":"50","author":"Zhu","year":"2018","journal-title":"Nat Genet"},{"key":"2024102102034453000_57.4.2002693.35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/carcin\/bgy006","article-title":"A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF\/interleukin-33","volume":"39","author":"Ding","year":"2018","journal-title":"Carcinogenesis"},{"key":"2024102102034453000_57.4.2002693.36","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200811-1730OC"},{"key":"2024102102034453000_57.4.2002693.37","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00510.2016"},{"key":"2024102102034453000_57.4.2002693.38","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jaci.2020.02.005","article-title":"Transcriptome-wide and differential expression network analyses of childhood asthma in nasal epithelium","volume":"146","author":"Forno","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2024102102034453000_57.4.2002693.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature14132"},{"key":"2024102102034453000_57.4.2002693.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005378"},{"key":"2024102102034453000_57.4.2002693.41","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"2024102102034453000_57.4.2002693.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802741106"},{"key":"2024102102034453000_57.4.2002693.43","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200809-1436OC"},{"key":"2024102102034453000_57.4.2002693.44","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1111\/all.13499","article-title":"17q21 variant increases the risk of exacerbations in asthmatic children despite inhaled corticosteroid use","volume":"73","author":"Farzan","year":"2018","journal-title":"Allergy"},{"key":"2024102102034453000_57.4.2002693.45","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9712108"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.02693-2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:30:09Z","timestamp":1740375009000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.02693-2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,1]]},"published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1183\/13993003.02693-2020"],"URL":"https:\/\/doi.org\/10.1183\/13993003.02693-2020","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]}}}