| 1. |
- Lemonnier, Nathanaël, et al.
(author)
-
A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
-
In: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Medsker, Brock H, et al.
(author)
-
Maternal depressive symptoms, maternal asthma, and asthma in school-aged children
- 2017
-
In: Annals of Allergy, Asthma & Immunology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1081-1206. ; 118:1, s. 55-U146
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Little is known about the joint effects of maternal asthma and maternal depression on childhood asthma. OBJECTIVE: To examine whether maternal depression and maternal asthma lead to greater risk of childhood asthma than maternal asthma alone. METHODS: Cross-sectional studies of children (6-14 years old) in San Juan, Puerto Rico (n = 655) and Sweden (n = 6,887) were conducted. In Puerto Rico, maternal depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire. In Sweden, maternal physician-diagnosed depression was derived from national registries, and maternal depressive symptoms were defined using an abbreviated CES-D questionnaire. Childhood asthma was defined as physician-diagnosed asthma plus current wheeze (in Puerto Rico) or plus medication use (in Sweden). Logistic regression was used for multivariable analysis. RESULTS: Compared with Puerto Rican children whose mothers had neither asthma nor depressive symptoms, those whose mothers had asthma but no depressive symptoms had 3.2 times increased odds of asthma (95% confidence interval [CI] = 2.1-4.8) and those whose mothers had asthma and depressive symptoms had 6.5 times increased odds of asthma (95% CI = 3.3-13.0). Similar results were obtained for maternal depression and maternal asthma in the Swedish cohort (odds ratio for maternal asthma without maternal depression = 2.8, 95% CI = 2.1-3.7; odds ratio for maternal asthma and maternal depression = 4.0, 95% CI = 1.7-9.6). Although the estimated effect of maternal asthma on childhood asthma was increased when maternal depressive symptoms (Puerto Rico) or maternal depression (Sweden) was present, there were no statistically significant additive interactions. CONCLUSION: Maternal depression can further increase the risk of asthma in children whose mothers have a history of asthma.
|
|
