Association Between Exposome, Deoxyribonucleic Acid (DNA) Damage and Asthma in Colombian Children Aged 2 to 4 Years
Bibliographic record
Abstract
Abstract RATIONALE: Asthma is a disease that affects millions of people worldwide and is the most prevalent childhood illness. Its pathophysiology is still not fully understood, and environmental exposures along with gene-environment interactions have been identified as major contributing factors to various diseases. This study aimed to determine the contribution of early-life exposome and DNA damage to asthma, as well as the modifying effect of genetic polymorphisms. METHODS: This is an analysis from the PROMESA cohort conducted in two of the most populous Colombian cities, involving children aged 2 to 4 years. The asthma diagnosis was made by pediatric pulmonologists following a standardized protocol. Genotyping was performed to evaluate the modifying effect of genetic polymorphisms (GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2) using PCR and PCR-RFLP. The early-life exposome was estimated through geographic information systems, remote sensing, LUR models, and questionnaires. The association between the exposome and asthma was estimated using Elastic Net Poisson regression with a log link and adjusted by ancestry and covariates. Interactions were identified with ExWAS. RESULTS: In 2022, 506 children (median age: 3.7 years) were studied. Asthma prevalence in 407 children was 37% (95% CI: 32.6–41.9). DNA damage was consistent regardless of asthma or acute respiratory infections presence but was higher in children with asthma in Medellín than in Bogotá (Figure 1). Exposures to dogs at home, weekly cereal intake, NO₂ during the first year, street connectivity, and recent home renovations reduced asthma prevalence by 6-29%. Conversely, curtains/carpets at home and building density within 300 m increased asthma risk by 6-54% (PR: 1.54 [1.24-1.90]). ExWAS identified 41 gene-exposome interactions (p < 0.05), with three remaining significant: home reconstructions with P53 (null vs. present), proximity to roads with GSTT1 (null vs. present), and carpets with GSTT1 (null vs. present) (see last column Table 1)CONCLUSIONS: The interaction between exposome and genetic polymorphisms is complex in children with asthma. DNA damage was greater in children in Medellín, where disease prevalence was also higher, highlighting the role of environmental factors in pediatric asthma pathophysiology. Results indicate that not only indoor exposure can influence Asthma, but also exposure at neighborhood and city level, such as urban environment and air pollution. Genetic variants in DNA repair and antioxidant defense may modulate this exposure-asthma relation. These findings can guide health professionals in assessing pediatric patients and providing environmental, dietary, and housing recommendations to prevent chronic diseases like asthma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".