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Record W3112934918 · doi:10.1016/j.jaci.2020.11.044

Shared DNA methylation signatures in childhood allergy: The MeDALL study

2020· review· en· W3112934918 on OpenAlexaff
Cheng‐Jian Xu, Olena Gruzieva, Cancan Qi, Ana Esplugues, Ulrike Gehring, Anna Bergström, Dan Mason, Leda Chatzi, Daniela Porta, Karin C. Lødrup Carlsen, Nour Baïz, Anne‐Marie Madore, Harri Alenius, Bianca van Rijkom, Soesma A. Jankipersadsing, Pieter van der Vlies, Inger Kull, Marianne van Hage, Mariona Bustamante, Aitana Lertxundi, Matías Torrent, Gillian Santorelli, Maria Pia Fantini, Vegard Hovland, Giancarlo Pesce, Nanna Fyhrquist, Tiina Laatikainen, Martijn C. Nawijn, Yang Li, Cisca Wijmenga, Mihai G. Netea, Jean Bousquet, Josep M. Antó, Catherine Laprise, Tari Haahtela, Isabella Annesi‐Maesano, Kai-Häkon Carlsen, Davide Gori, Manolis Kogevinas, John Wright, Cilla Söderhäll, Judith M. Vonk, Jordi Sunyer, Erik Melén, Gerard H. Koppelman

Bibliographic record

VenueJournal of Allergy and Clinical Immunology · 2020
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsCentre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-JeanUniversité du Québec à Chicoutimi
FundersFP7 HealthNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Institute of Environmental Health SciencesEuropean Commission
KeywordsDNA methylationAllergyCpG siteAsthmaEpigeneticsMethylationImmunologyDifferentially methylated regionsMedicineBiologyGeneticsGeneGene expression

Abstract

fetched live from OpenAlex

BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.008
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.038
GPT teacher head0.363
Teacher spread0.325 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations39
Published2020
Admission routes1
Has abstractyes

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