Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy
Bibliographic record
Abstract
Background Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. Objective We sought to investigate genetic susceptibility to PA. Methods Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. Results An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA ( P = 1.80 × 10 −8 ), whereas SNPs associated with Src kinase–associated phosphoprotein 1 (SKAP1) , matrix metallopeptidase 12 (MMP12)/MMP13 , catenin α3 (CTNNA3) , rho GTPase–activating protein 24 (ARHGAP24) , angiopoietin 4 (ANGPT4) , chromosome 11 open reading frame (C11orf30/EMSY) , and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association ( P ≤ 1.49 × 10 −6 ). In the meta-analysis of PA, loci in or near ITGA6 , ANGPT4 , MMP12/MMP13 , C11orf30 , and EXOC4 were significant ( P ≤ 1.49 × 10 −6 ). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance ( P = 7.50 × 10 −11 ), whereas SNPs associated with ITGA6 , ANGPT4 , MMP12/MMP13 , and EXOC4 and additional C11orf30 SNPs were suggestive ( P ≤ 1.49 × 10 −6 ). Functional annotation indicated that SKAP1 regulates expression of CBX1 , which colocalizes with the EMSY protein coded by C11orf30. Conclusion This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes ( C11orf30 / EMSY , SKAP1 , and CTNNA3 ) identified by this study are involved in epigenetic regulation of gene expression.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".