Genome‐wide association study of body mass index in 23 000 individuals with and without asthma
Bibliographic record
Abstract
Summary Background Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co‐morbidity between these conditions. Objective To identify genetic variants that are associated with body mass index ( BMI ) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. Methods In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. In total, 19 studies contributed with genome‐wide analysis study ( GWAS ) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. Results We report associations between several DENND 1B variants ( P = 2.2 × 10 −7 for rs4915551) on chromosome 1q31 and BMI from a meta‐analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND 1B single nucleotide polymorphisms ( SNP s) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated ( P < 0.05) in two of the seven studies and of borderline significance in one ( P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m 2 ( P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND 1B SNP . FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. Conclusions and Clinical Relevance DENND 1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND 1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND 1B points to complex associations with the studied diseases that deserve further study.
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.001 | 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) | 0.003 | 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".