Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.
Bibliographic record
Abstract
Obsessive-compulsive disorder (OCD) affects ~1% of the population and<br> exhibits a high SNP-heritability, yet previous genome-wide association<br> studies (GWAS) have provided limited information on the genetic etiology<br> and underlying biological mechanisms of the disorder. We conducted a<br> GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls<br> from 28 European-ancestry cohorts revealing 30 independent genome-wide<br> significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for<br> clinical, biobank, comorbid, and self-report sub-groups found no<br> evidence of sample ascertainment impacting our results. Functional and<br> positional QTL gene-based approaches identified 249 significant<br> candidate risk genes for OCD, of which 25 were identified as putatively<br> causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region.<br> Tissue and single-cell enrichment analyses highlighted hippocampal and<br> cortical excitatory neurons, along with D1- and D2-type dopamine<br> receptor-containing medium spiny neurons, as playing a role in OCD risk.<br> OCD displayed significant genetic correlations with 65 out of 112<br> examined phenotypes. Notably, it showed positive genetic correlations<br> with all included psychiatric phenotypes, in particular anxiety,<br> depression, anorexia nervosa, and Tourette syndrome, and negative<br> correlations with a subset of the included autoimmune disorders,<br> educational attainment, and body mass index.. This study marks a<br> significant step toward unraveling its genetic landscape and advances<br> understanding of OCD genetics, providing a foundation for future<br> interventions to address this debilitating disorder.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.003 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.005 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.011 | 0.003 |
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; both teacher heads agree on what is shown here.
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".