P359: Early-onset psychosis: Exploring the psychological phenotype of DLG4-related synaptopathy
Bibliographic record
Abstract
PCR-confirmed SARS-CoV-2 patients were enrolled in the GENCOV study.We defined inpatients as being admitted for management of severe COVID-19, and compared SNPs to those not requiring hospitalization.The enrichment of effect alleles in hospitalized vs non-hospitalized individuals was compared by Pearson's X 2 or Fisher's exact test, as appropriate.We used multiple logistic regression analysis [Odds Ratio (OR) with 95% confidence interval (CI)] to assess the confounding effects of age, sex, and ancestry, as well as the direction of the association.Bonferroni correction (Pc) was done to account for multiple testing for twenty-six SNPs with statistical significance set at P0.00192.Results: Genome sequencing was performed on 1,108 samples [median age: 50 years (IQR: 36-63), 523 (47.2%) are male, and 261 (23.6%) were hospitalized].Initially, we assessed the association of socio-demographic factors commonly associated with COVID-19 clinical outcome -hospitalization.The proportion of individuals who were hospitalized and aged 60 years, male, and non-White ancestry was 54.7%, 31.2%, and 34.2%, respectively.Thus, age 60 years (OR=12.04,95% CI: 8.70-16.66),male sex (OR=2.25,95% CI: 1.69-2.99),and non-White ancestry (OR=13.75,95% CI: 7.89-23.96)were all associated significantly with increased risk of hospitalization.Despite the small sample size, two out of the twenty-six SNPs analyzed showed significant association with hospitalization.After adjusting for age, sex, and ancestry LZTFL1 [rs11385942, ), Pc=3.51x10 -9 ], and TLR7 [rs3853839, OR=2.05 (1.24-3.41),Pc=3.20x10 -4 ] were both associated with an increased risk for hospitalization.Conclusion: Our study illustrates that genetic variation plays a significant role in the host response to SARS-CoV-2 infection, and influences COVID-19 clinical outcomes.The LMNA variant has been linked with neutropenia among COVID-19 patients, LZTFL1 promotes airway ciliogenesis, and TLR7 is implicated in the interferon pathway.Fine-mapping to identify the causal variation in linkage-disequilibrium to the associated SNPs may help to further unravel the mechanistic factors associated with COVID-19 clinical outcomes and lead to therapeutic interventions.To achieve significant statistical power, GENCOV data was contributed to the Canadian HostSeq and to the HGI for further study.
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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) | 0.000 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".