Transcriptomics of Atopy and Atopic Asthma in White Blood Cells from Children and Adolescents

Jiang, Yangzi; Gruzieva, Olena; Wang, T.; Forno, Erick; Boutaoui, Nadia; Sun, Tao; Acosta‐Pérez, Edna; Canino, G.; Melén, E.; Chen, W.; Celedón, Juan C.

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a1058

Cited by 2 publications

(5 citation statements)

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“…We examined gene expression of single diseases and multimorbidity. We replicated the results in the Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA‐PR) cohort 9 . To our knowledge, the present study constitutes to date the largest comprehensive whole blood gene expression dataset on allergy and the first assessment of multimorbidity molecular signatures.…”

Section: Introductionsupporting

confidence: 75%

“…The results for multimorbidity were consistent in particular since the replication cohort was from a different environment (Puerto Rico), and RNA Sequencing on white blood cells was used 9,21 . For example, the log 2 FC value for CLC in discovery is 0.44 in any multimorbidity (expression increased by 36% in allergic participants compared to controls), and 0.14 in replication (10% increase).…”

Section: Discussionmentioning

confidence: 60%

“…Relative expression of a randomly selected subset of eight genes was assessed by reverse transcription quantitative polymerase chain reaction (RT‐qPCR). The replication arm was performed for DEGs in any multimorbidity, rhinitis alone and asthma alone in the EVA‐PR cohort, 9 using RNA Sequencing. We retrieved co‐expressed genes with weighted gene co‐expression network analysis (WGCNA).…”

Section: Methodsmentioning

confidence: 99%

“…No study assessed multimorbidity using transcriptomics. Genes and pathways for atopy and atopic asthma in children and adolescents were found using transcriptome‐wide data from peripheral blood 9 …”

Section: Introductionmentioning

confidence: 99%

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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents

Lemonnier

Melén

Jiang

et al. 2020

Allergy

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Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease. Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found. Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.

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Section: Introductionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents

Lemonnier

Melén

Jiang

et al. 2020

Allergy

View full text Add to dashboard Cite

show abstract

“…Moreover, ocular symptoms add further complexity to the allergy phenotypes (22) and to SA (23). By combining big data analyses [MASK (3)], classical epidemiologic studies, in silico analyses, transcriptomics [MeDALL (21,24,25)] and gene sequencing (26), the mechanisms of allergic diseases have been reclassified. In particular, polysensitization and multimorbidity represent the extreme allergic phenotype, starting early in life and with the greatest severity.…”

Section: New Concepts Of Allergic Multimorbiditymentioning

confidence: 99%