Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study

Hoang, Thanh T.; Sikdar, Sinjini; Xu, Cheng‐Jian; Lee, Mi Kyeong; Cardwell, Jonathan; Forno, Erick; Imboden, Medea; Jeong, Ayoung; Madore, Anne-Marie; Qi, Cancan; Wang, Tianyuan; Bennett, Brian D.; Ward, James M.; Parks, Christine G.; Freeman, Laura E. Beane; King, Debra; Motsinger‐Reif, Alison A.; Umbach, David M.; Wyss, Annah B.; Schwartz, David A.; Celedón, Juan C.; Laprise, Catherine; Ober, Carole; Probst‐Hensch, Nicole; Yang, Ivana V.; Koppelman, Gerard H.; London, Stephanie J.

doi:10.1183/13993003.00217-2020

Cited by 44 publications

(44 citation statements)

References 58 publications

(67 reference statements)

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“…IgE sensitization to food and airborne allergens usually starts during early childhood and is for many children the first step in the progression to clinical manifestations such as atopic eczema, food allergy, seasonal or perennial rhinitis, and/or asthma [ 4 ]. In recent years, some studies have evaluated the association between DNA methylation and the development of allergen-specific IgE sensitization [ 5 , 6 , 7 , 8 , 9 ]. However, the cross-sectional design of these studies imposes the limitation that it is not possible to know if the observed DNA methylation differences are a consequence of the ongoing atopic reactions or precede the inception of immunoglobulin E (IgE) sensitization.…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

Acevedo

Scala²,

Merid

et al. 2021

IJMS

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DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

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Section: Introductionmentioning

confidence: 99%

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

Acevedo

Scala²,

Merid

et al. 2021

IJMS

Self Cite

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“…An Epigenome-Wide Association Study found that STX6 may one of genes that associated with atopic asthma. They also reported that STX6 may has a role in methylate process that is seen in this disease (28) In other studies, the association between PLCB1 and the decrease of FEV1 and FEV1/FVC in their participation was shown (29). Another study reported that PLCB1 at least in two pedigree with severe COPD was observed (30) Other group found an association between ZNF33A gen and remission from asthma(31) LARP4B is a target gene of miR106 inhibition of miR-106b that suppressed the mRNA and protein expression of cancer-related genes (32).…”

Section: Discussionmentioning

confidence: 86%

Identification of Novel Genes Associated with Chronic Obstructive Pulmonary Disease Using Different Penalized Logistics Regression with High-Dimensional Biological Data from Human Sputum Cells

Gohari

Kazemnejad

Mostafaei

et al. 2021

Preprint

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Background: Comparison of LASSO, smoothly clipped absolute deviation (SCAD) and minimax concave penalty (MCP) logistic classifiers in order to reconnaissance of related genes with COPD disease and assessing the genes effects on the progression of the disease based on one of the main classes of cells involved in the disease, Sputum Cells. We used a genome-wide expression profiling to define gene networks relevant to the disease. The data retrieved from Gene Expression Omnibus (GEO) with accession numbers "GSE22148". From 143 samples in GOLD stage 2-4 COPD ex-smokers, 54,675 probes primary were assessed. After normalization, LASSO, SCAD and MCP logistic regressions were applied. K-fold cross-validation scheme was used to evaluate the performance of two methods. All of the computational processes were done using "ncvreg", "Affy," "Limma" and "SVA" R packages. Results: The results of LASSO (AUC=0.95, sensitivity= 0.91, specificity= 0.86) and SCAD (AUC=0.97, sensitivity= 0.95, specificity= 0.85) logistic regression were almost similar. There were 23 and 22 significantly associated genes for LASSO and SCAD, respectively. The only difference between these models is related to "stromal interaction molecule 2". Comparing to MCP approach, the most conservative method, we detected only 7 significant genes (AUC= 0.94, sensitivity= 0.94, specificity= 0.82). Conclusions: In the present study, the relative expressions of thousands of the genes were assessed and identified as associated genes with the progression of COPD. Differential analysis of gene expression data is able to reduce the number of genes but in a limited manner. In order to find an efficient and small subset of genes, we should use alternative approaches like logistic regression. Regularization solves the high dimensionality problem in using this kind of regression.

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“…Consequently, CLC was included in transcriptomic cluster TAC1 of patients with high sputum eosinophilia in the abovementioned U-BIOPRED asthma study 37 and associated with asthma in an epigenome-wide association study (EWAS) 44 .…”

Section: Charcot-leyden Crystal Protein (Clc)mentioning

confidence: 99%

“…Since IL13-stimulated parkin aids mono-ubiquitination of EPS15 thus preventing RTKs internalization and potentializing the effects of TGF-b, it forms a link between the two pro-brotic cytokines as well as mtDNA-mediated in ammation. EPS15L1, a protein of suggested role in the process of receptor endocytosis, coimmunoprecipitates with EPS15 and is one of the genes associated with asthma in an EWAS study 44 and EPS15 transcript is upregulated in human ASM cells upon their stimulation 87 .…”

Section: Deiodinase Iodothyronine Type III (Dio3)mentioning

confidence: 99%

Integration of Airway Inflammation and Remodeling Mechanisms Specific to Eosinophilic Asthma Through Differential Co-Expression of Genes in Bronchial Brush Biopsy Samples

Koźlik

Buregwa-Czuma

Zawlik

et al. 2021

Preprint

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Background Heterogeneity of asthma complicates search for targeted treatment against airway hyperresponsiveness and remodeling. We conducted a systems biology approach study to establish differential co-expression of genes (DCG) in eosinophilic and non-eosinophilic asthma patients and infer their role in the disease. Materials and Methods N = 40 Caucasian adult moderate to severe non-smoking asthma patients (half with eosinophilic asthma) undergone bronchial brush biopsy sampling for mRNA expression using hybridization to cDNA microarray. Mechanistic interpretation of DCG was inferred from existing literature. Results Differentially co-expressed genes bear significance in airway viral infection (ATP1B1, EPS15), arachidonic acid metabolism (CLC, FADS6), cell migration (EPS8L1, STOML3, RhoBTB2), surface receptors endocytosis (STRN4, EPS15, ATP1B1) or decreased expression (CCT7), oxidative stress (DIO3, RhoBTB2), decreased adhesion (ATP1B1, RAPH1, STOML3), epithelial-mesenchymal transition (ASB3, RADX, CCT7, MRPL14, PPP2R3B, RPS13, SLC19A1), myofibroblast differentiation (CCT7), smooth muscle proliferation (ASB3, ATP1B1), airway hyperreactivity (RECK, STOML3, ATP1B1, OR52I1), extracellular matrix remodeling (FBN3, RECK), angiogenesis (GPI, RhoBTB2) and neuronal pathogenesis of asthma (OR52I1, STRN4, TTC3P1, GPI, CABP5) and were linked to asthma in genome- (MRPL14, ASB3, RPS13) and epigenome-wide (CLC, EPS15, GPI, SSCRB4, STRN4) association studies. Signaling pathways involved (especially TGF-β/Smad2/3) are inferred from the co-expression pattern. Conclusion Activity of genes and pathways of known or tentative role in asthma pathogenesis was established in regard to a condition cognizable in clinical practice.

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Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study

Cited by 44 publications

References 58 publications

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

Identification of Novel Genes Associated with Chronic Obstructive Pulmonary Disease Using Different Penalized Logistics Regression with High-Dimensional Biological Data from Human Sputum Cells

Integration of Airway Inflammation and Remodeling Mechanisms Specific to Eosinophilic Asthma Through Differential Co-Expression of Genes in Bronchial Brush Biopsy Samples

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