Influence of Genome-wide Variation on Complex Disease Risk in 22q11.2 Deletion Syndrome
Bibliographic record
Abstract
The 22q11.2 deletion has been associated with increased risk for many complex disorders. Mechanisms underlying its variable expression, however, are not well understood. In this thesis, I test the hypothesis that genome-wide variation may influence the expression of schizophrenia and lipid metabolism disorders in individuals with a 22q11.2 deletion. We hypothesized that 22q11.2 deletion-related microRNA dysregulation may exacerbate schizophrenia risk associated with additional rare copy number variants (CNVs). Consistent with this hypothesis, we found that individuals with schizophrenia were about twice as likely versus those without to have an additional rare CNV overlapping a gene targeted by a microRNA. In our study of lipid levels, we identified two pathogenic rare variants, and an association between polygenic risk scores and lipid levels. Collectively, these results support the role of genome-wide variation in modifying the expression of the 22q11.2 deletion and implicate cellular mechanisms that may contribute to these complex disorders.
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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 | 0.000 | 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) | 0.002 | 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".