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Transcriptomics of atopy and atopic asthma in white blood cells from children and adolescents.
Jiang, Yale; Gruzieva, Olena; Wang, Ting; Forno, Erick; Boutaoui, Nadia; Sun, Tao; Merid, Simon K; Acosta-Pérez, Edna; Kull, Inger; Canino, Glorisa; Antó, Josep M; Bousquet, Jean; Melén, Erik; Chen, Wei; Celedón, Juan C.
Afiliação
  • Jiang Y; Division of Pulmonary Medicine, Dept of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
  • Gruzieva O; School of Medicine, Tsinghua University, Beijing, China.
  • Wang T; These two authors contributed equally to this work.
  • Forno E; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Boutaoui N; These two authors contributed equally to this work.
  • Sun T; Division of Pulmonary Medicine, Dept of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
  • Merid SK; Division of Pulmonary Medicine, Dept of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
  • Acosta-Pérez E; Division of Pulmonary Medicine, Dept of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kull I; Dept of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Canino G; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Antó JM; Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.
  • Bousquet J; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Melén E; Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.
  • Chen W; ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.
  • Celedón JC; CESP, Inserm U1018, Villejuif, France.
Eur Respir J ; 53(5)2019 05.
Article em En | MEDLINE | ID: mdl-30923181
Early allergic sensitisation (atopy) is the first step in the development of allergic diseases such as atopic asthma later in life. Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised.A transcriptome-wide association study (TWAS) of atopy and atopic asthma in white blood cells (WBCs) or whole blood was conducted in a cohort of 460 Puerto Ricans aged 9-20 years (EVA-PR study) and in a cohort of 250 Swedish adolescents (BAMSE study). Pathway enrichment and network analyses were conducted to further assess top findings, and classification models of atopy and atopic asthma were built using expression levels for the top differentially expressed genes (DEGs).In a meta-analysis of the study cohorts, both previously implicated genes (e.g. IL5RA and IL1RL1) and genes not previously reported in TWASs (novel) were significantly associated with atopy and/or atopic asthma. Top novel genes for atopy included SIGLEC8 (p=8.07×10-13), SLC29A1 (p=7.07×10-12) and SMPD3 (p=1.48×10-11). Expression quantitative trait locus analyses identified multiple asthma-relevant genotype-expression pairs, such as rs2255888/ALOX15 Pathway enrichment analysis uncovered 16 significantly enriched pathways at adjusted p<0.01, including those relevant to T-helper cell type 1 (Th1) and Th2 immune responses. Classification models built using the top DEGs and a few demographic/parental history variables accurately differentiated subjects with atopic asthma from nonatopic control subjects (area under the curve 0.84).We have identified genes and pathways for atopy and atopic asthma in children and adolescents, using transcriptome-wide data from WBCs and whole blood samples.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Transcriptoma / Hipersensibilidade / Leucócitos Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Child / Female / Humans / Male País/Região como assunto: Caribe / Puerto rico Idioma: En Revista: Eur Respir J Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Transcriptoma / Hipersensibilidade / Leucócitos Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Child / Female / Humans / Male País/Região como assunto: Caribe / Puerto rico Idioma: En Revista: Eur Respir J Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido