DNA methylation and serum total immunoglobulin E (IgE) levels: a methylome-wide association study in adults with asthma
Bibliographic record
Abstract
<bold>Introduction:</bold> Asthma endotypes may be associated with specific epigenetic signatures. The identification of differentially methylated loci associated with serum total IgE levels in adults with asthma may bring further insight into asthma heterogeneity. <bold>Objective:</bold> To identify differentially methylated regions associated with serum total IgE levels in adults with asthma. <bold>Methods:</bold> DNA methylation was measured in 599 blood samples from 357 adults with asthma participating to the EGEA cohort (241 individuals had 2 samples 10 years apart) using MethylC-Capture Sequencing. After quality control, 2.8 million CpG sites were analysed. A binomial mixed model was fitted for each CpG site, considering the proportion of methylated reads weighted for sequence read coverage as the dependent variable, IgE levels (log-transformed) as the predictor, and age, sex, active smoking, and proportion of leucocytes as confounders. At loci with CpG sites showing suggestive association with IgE levels at p<10<sup>-4</sup>, we used the Comb-p method to identify differentially methylated regions (DMRs). <bold>Results:</bold> Overall, 312 CpG sites were associated with IgE levels at p<10<sup>-4</sup>, but none was significant at FDR≤5%. 11 DMRs were detected at Sidak p<0.01; one of them at 22q11 included the <italic>IL17RA</italic> gene involved in signalling in airway inflammation, while another one at 13q34 harboured the <italic>TUBGCP3</italic> gene, previously suggested as an epigenetic mark in respiratory allergy. <bold>Conclusions:</bold> Using high-resolution methylome data, we identified DMRs associated with serum total IgE levels in adults with asthma, including biological relevant genes in the development of novel therapeutic targets or biomarkers for allergic asthma.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".