Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Lemonnier N

PROVIDER: S-EPMC9302020 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Lemonnier Nathanaël N Melén Erik E Jiang Yale Y Joly Stéphane S Ménard Camille C Aguilar Daniel D Acosta-Perez Edna E Bergström Anna A Boutaoui Nadia N Bustamante Mariona M Canino Glorisa G Forno Erick E Ramon González Juan J Garcia-Aymerich Judith J Gruzieva Olena O Guerra Stefano S Heinrich Joachim J Kull Inger I Ibarluzea Maurolagoitia Jesús J Santa-Marina Rodriguez Loreto L Thiering Elisabeth E Wickman Magnus M Akdis Cezmi C Akdis Mübeccel M Chen Wei W Keil Thomas T Koppelman Gerard H GH Siroux Valérie V Xu Cheng-Jian CJ Hainaut Pierre P Standl Marie M Sunyer Jordi J Celedón Juan C JC Maria Antó Josep J Bousquet Jean J

Allergy 20200423 12

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32277847

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Project description:Several studies have reported negative relations between allergic diseases and school performance but have not simultaneously considered various allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, and only examined a limited number of participants. The present study investigated the associations of allergic rhinitis, asthma, and atopic dermatitis with school performance in a large, representative Korean adolescent population. A total of 299,695 7th through 12th grade students participated in the Korea Youth Risk Behaviour Web-based Survey (KYRBWS) from 2009 to 2013. The subjects' history of allergic rhinitis, asthma, and atopic dermatitis and number of school absences due to these diseases in the previous 12 months were examined and compared. School performance was classified into 5 levels. The relations between allergic disorders and school performance were analyzed using multiple logistic regressions with complex sampling and adjusted for the subjects' durations of sleep, days of physical activity, body mass indexes (BMIs), regions of residence, economic levels, parents' education levels, stress levels, smoking status, and alcohol use. A subgroup analysis of the economic groups was performed. Allergic rhinitis was positively correlated with better school performance in a dose-dependent manner (adjusted odds ratios, AOR, [95% confidence interval, CI] = 1.50 [1.43-1.56 > 1.33 [1.28-1.38] > 1.17 [1.13-1.22] > 1.09 [1.05-1.14] for grades A > B > C > D; P < 0.001). Asthma was negatively correlated with better school performance (AOR [95% CI] = 0.74 [0.66-0.83], 0.87 [0.79-0.96], 0.83 [0.75-0.91], 0.93 [0.85-1.02] for performance A, B, C, and D, respectively; P < 0.001). Atopic dermatitis was not significantly correlated with school performance. The subgroup analysis of the students' economic levels revealed associations between allergic diseases and school performance. Compared to other allergic disorders, the asthma group had more school absences due to their symptoms (P < 0.001). School performance was positively correlated with allergic rhinitis and negatively correlated with asthma in Korean adolescents, even after adjusting for other variables. The asthma group had an increased number of school absence days, which presumably contributes to these students' poor school performance.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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