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Transcriptomics of atopy and atopic asthma in white blood cells from children and adolescents
Selasa, 14 Mei 2019 16:08:10

Yale JiangOlena GruzievaTing WangErick FornoNadia BoutaouiTao SunSimon K. MeridEdna Acosta-PérezInger KullGlorisa CaninoJosep M. AntóJean BousquetErik MelénWei ChenJuan C. Celedón

European Respiratory Journal 2019; DOI: 10.1183/13993003.00102-2019

Abstract

Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised.

A transcriptome-wide association study of atopy and atopic asthma in white blood cells or whole blood was conducted in a cohort of 460 Puerto Ricans aged 9–20 years (EVA-PR) and in a cohort of 250 Swedish adolescents (BAMSE). 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.

In a meta-analysis of the study cohorts, both previously implicated genes (e.g.IL5RA and IL1RL1) and genes not previously reported in TWAS (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 (eQTL) analyses identified multiple asthma-relevant genotype-expression pairs, such as rs2255888/ALOX15. Pathway enrichment analysis uncovered sixteen significantly enriched pathways at p<0.01, including those relevant to Th1 and Th2 immune responses. Classification models built using the top differentially expressed genes and a few demographic/parental history variables accurately differentiated subjects with atopic asthma from non-atopic 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 white blood cells and whole blood samples.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Celedon reports other from GSK, Merck, and Pharmavite, outside the submitted work.

Conflict of interest: Dr. BOUSQUET reports personal fees and other from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, Uriach, other from Kyomed, from null, outside the submitted work.

Conflict of interest: Dr. Chen has nothing to disclose.

Conflict of interest: Dr. Melén has nothing to disclose.

Conflict of interest: Dr. Jiang has nothing to disclose.

Conflict of interest: Dr. Wang has nothing to disclose.

Conflict of interest: Dr. Forno has nothing to disclose.

Conflict of interest: Dr. Boutaoui has nothing to disclose.

Conflict of interest: Dr. Sun has nothing to disclose.

Conflict of interest: Dr. Merid has nothing to disclose.

Conflict of interest: Dr. Antó has nothing to disclose.

Conflict of interest: Dr. Canino has nothing to disclose.

Conflict of interest: Dr. Gruzieva has nothing to disclose.

Conflict of interest: Dr. Acosta-Pérez has nothing to disclose.

Conflict of interest: Dr. Kull has nothing to disclose.