<i>De novo</i> variant analysis of childhood-onset obsessive-compulsive disorder in the French-Canadian population
Bibliographic record
Abstract
Abstract Childhood-onset obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with a strong genetic component. De novo variants (DNVs) have been shown to have a role in childhood-onset OCD, but to date, no DNV analysis has been performed in patients from a genetically isolated population. Here, we aimed to investigate the impact of rare de novo single nucleotide variants (dnSNVs) on childhood-onset OCD risk in the French-Canadian population. In a cohort of 36 French-Canadian trios comprised of 36 probands with childhood-onset OCD and 72 unaffected parents, we identified 34 dnSNVs harboured in 34 different genes. We found that four of these genes were previously associated with OCD, replicating their contribution to its risk. We also observed complete overlap between our 34 candidate genes and genes associated with 11 related neuropsychiatric disorders, supporting a shared underlying genetic susceptibility across psychopathologies. Among genes harbouring DNVs across three childhood-onset OCD cohorts, we observed an overrepresentation of genes involved in clathrin-dependent endocytosis (GO:0072583; p-adj = 0.0498) and phosphatidylinositol binding (GO:0035091; p-adj = 0.0431), offering potential biological mechanisms underlying childhood-onset OCD. No association was found between the number of dnSNVs in childhood-onset OCD probands and OCD symptom severity. Altogether, this study offers a framework for performing DNV analyses of complex disorders in genetically isolated populations. We have provided the first list of candidate childhood-onset OCD genes in the French-Canadian population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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 teacher head, 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".