ArticleProceedings of the National Academy of Sciences of the United States of America2022
DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Pathway-level epigenetic modeling illuminates the methylation architecture to asthma risk across tissues.Epigenetics & chromatin · 2026Article
- Article
- How Epigenetics Bridges Genes and Environment: A Multiomics Evidence Chain in Congenital Diaphragmatic Hernia.Birth defects research · 2026Review
- Integrated transcriptomic analysis identifies tsRNA-mRNA regulatory axis in asthma pathogenesis.The World Allergy Organization journal · 2026Article
- Airway epithelial dysfunction in asthma pathogenesis: epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities.Frontiers in allergy · 2026Review
- Programming of the respiratory epitheliummedRxiv : the preprint server for health sciences · 2025Article
- Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections.International journal of molecular sciences · 2025Review
- Genetic contributions to epigenetic-defined endotypes of allergic phenotypes in children.American journal of human genetics · 2025Article
- Multi-trait genetic analysis of asthma and eosinophils uncovers pleiotropic loci in East Asians.Nature communications · 2025Article
- Epigenetic ageing clocks: statistical methods and emerging computational challenges.Nature reviews. Genetics · 2025Review
- Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer.Genome medicine · 2025Article
- Maternal asthma imprints fetal lung ILC2s via glucocorticoid signaling leading to worsened allergic airway inflammation in murine adult offspring.Nature communications · 2025Article
- European Respiratory Society Research Seminar on Preventing Pediatric Asthma.Pediatric pulmonology · 2025Review
- Co-Expression Network and Machine Learning Analysis of Transcriptomics Data Identifies Distinct Gene Signatures and Pathways in Lesional and Non-Lesional Atopic Dermatitis.Journal of personalized medicine · 2024Article
- Development of an epigenetic clock resistant to changes in immune cell composition.Communications biology · 2024Article
- Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.Nature communications · 2024Article
- Epigenetic Approaches to Identifying Asthma Endotypes.Allergy, asthma & immunology research · 2024Review
- Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function.Clinical epigenetics · 2024Article
- Epigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study.Nature communications · 2023Article
- Recent progress in the genetic and epigenetic underpinnings of atopy.The Journal of allergy and clinical immunology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Maternal asthma (MA) is among the most consistent risk factors for asthma in children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 nonasthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene coexpression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA and MA cases, respectively, compared with controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five comethylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared with NMA cases (P = 7.1 × 10−3), a finding that replicated in nasal epithelial cells from an independent cohort (P = 0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum immunoglobulin E, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that MA alters diverse epigenetically mediated pathways that lead to distinct subtypes of severe asthma in adults, including hard-to-treat T2-low asthma.
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