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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorHerrera-Luis, Esther
dc.contributor.authorOrtega, Victor E.
dc.contributor.authorAmpleford, Elizabeth J.
dc.contributor.authorSio, Yang Yie
dc.contributor.authorGranell, Raquel
dc.contributor.authorde Roos, Emmely
dc.contributor.authorCruz Carmona, Mª Jesús
dc.date.accessioned2022-09-12T10:26:11Z
dc.date.available2022-09-12T10:26:11Z
dc.date.issued2022-06
dc.identifier.citationHerrera-Luis E, Ortega VE, Ampleford EJ, Sio YY, Granell R, Roos E de, et al. Multi-ancestry genome-wide association study of asthma exacerbations. Pediatr Allergy Immunol. 2022 Jun;33(6):e13802.
dc.identifier.issn1399-3038
dc.identifier.urihttp://hdl.handle.net/11351/8166
dc.descriptionAsthma exacerbations; Single-nucleotide polymorphism
dc.description.abstractBackground Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10−5) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele) = 0.82, p = 9.05 × 10−6 and replication: ORT allele = 0.89, p = 5.35 × 10−3) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele = 0.85, p = 3.10 × 10−5 and replication: ORC allele = 0.89, p = 1.30 × 10−2). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofseriesPediatric Allergy and Immunology;33(6)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectAsma - Aspectes genètics
dc.subjectGenòmica
dc.subjectPolimorfisme genètic
dc.subject.meshGenome-Wide Association Study
dc.subject.meshAsthma
dc.subject.mesh/genetics
dc.subject.meshPolymorphism, Single Nucleotide
dc.titleMulti-ancestry genome-wide association study of asthma exacerbations
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1111/pai.13802
dc.subject.decsestudio de asociación genómica completa
dc.subject.decsasma
dc.subject.decs/genética
dc.subject.decspolimorfismo de nucleótido único
dc.relation.publishversionhttps://doi.org/10.1111/pai.13802
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Herrera-Luis E] Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain. [Ortega VE] Division of Respiratory Medicine, Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA. [Ampleford EJ] Department of Internal Medicine, Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. [Sio YY] Department of Biological Sciences, National University of Singapore, Singapore City, Singapore. [Granell R] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [de Roos E] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. [Cruz MJ] CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35754128
dc.identifier.wos000820316700004
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/SAF2017-83417R
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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