Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2018
Bibliographic record
Abstract
Background: Earlier studies have evaluated that genetics contribute to 55-74% of asthma heritability, of which only small percentage may be explained by known loci [1].We hypothesize that the missing heritability lies within interactions among genes as well as between genes with environmental exposures.Using genomics data from the Canadian Healthy Infant Longitudinal Development study (CHILD; N = 3455) [2], we hereby investigate the effects of common and rare variants as well as their interactions with modifiable exposures on risk of recurrent wheeze during early childhood.Methods: We ascertained genomics data using the Illumina Human-CoreExome BeadChip.After quality control assessments and imputations, 22 million variants from 2830 children were included for analysis.Recurrent wheeze, a clinical outcome strongly correlated with asthma, reported from age 2 to 5 was used as the primary phenotype in our analysis.Results: Our genome-wide association study (GWAS) identified loci on chromosome 17q12, a highly replicated loci for asthma, associated with recurrent wheeze.Genetic risk score analysis (GRS) and SNPset kernel association test (SKAT), which calculates the accumulated effect of common and rare variations, respectively, identified sets of variants significantly associated with recurrent wheeze in childhood.Gene-environment interaction analysis identified variations correlated with increased wheeze prevalence in children who were exposed to prenatal smoking.Finally, gene-gene (i.e.epistatic) interactions were studied by constructing a network of inter-correlated variants via hierarchical clustering, a machine learning algorithm for grouping similar elements.This analysis identified 8 clusters of interacting genes linked with childhood wheeze.Conclusion: Our results show that both genes and environmental exposures contribute to recurrent wheeze in children as young as age 2, which is associated with asthma diagnosis later in childhood.Ongoing analyses include additional asthma-related phenotypes such as longitudinal lung function and positive skin prick tests to allergens as well as environmental variables such as pet ownership and nutrition.
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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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.004 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.274 | 0.122 |
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".