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- Lemonnier, Nathanaël, et al.
(författare)
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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Lyon, Helen N., et al.
(författare)
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The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts
- 2007
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples.
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| 3. |
- Medsker, Brock H, et al.
(författare)
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Maternal depressive symptoms, maternal asthma, and asthma in school-aged children
- 2017
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Ingår i: Annals of Allergy, Asthma & Immunology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1081-1206. ; 118:1, s. 55-U146
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Tidskriftsartikel (refereegranskat)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.
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