F192. SYSTEMATIC META-ANALYSIS IDENTIFIES FIVE NOVEL ASSOCIATION LOCI FOR SCHIZOPHRENIA
Bibliographic record
Abstract
Schizophrenia is a highly heritable psychiatric disorder. In the past 30 years, thousands of case-control and family-designed association studies have examined candidate genes for schizophrenia. To assist the field in interpreting this large volume of gene-association studies, the online SzGene database was created and included meta analyses for 287 polymorphisms at the time of its final update in 2010. However, since then more than one-thousand new gene-association studies in schizophrenia have been conducted. As such, we have conducted an updated systematic review and meta-analysis of all gene-association studies in schizophrenia published before March 2017. Studies published between January 2010 and March 2017 were identified using a customized querying strategy. Identified gene-association studies were included in the review and meta-analysis if they: 1) were case-control or family-designed studies with polymorphisms detected in schizophrenia or schizoaffective patients, 2) provide sufficient data to perform meta-analysis, and 3) were not genome-wide association studies (GWAS). Random-effects meta-analysis was performed on polymorphisms with four or more independent studies. Raw data of 1711 studies included in the SzGene database were integrated with 1368 studies identified from our systematic literature search. Random-effects meta-analysis were applied to 540 polymorphisms with at least four studies and 89 of these polymorphisms were nominally associated with SZ (unadjusted p < 0.05). After bonferroni correction, 12 polymorphisms remained statistically significant, including five associations not reported in the most recent Psychiatric Genomics Consortium schizophrenia GWAS: 1) rs11098403, p = 1.45e-10, odds ratio = 0.65; 2) rs12807809, p = 7.04e-06, odds ratio = 0.91; 3) rs910694 in PDE4B: p = 1.05e-05, odds ratio = 0.77; 4) rs1801133 in MTHFR: p = 2.99e-05, odds ratio = 1.13 and 5) rs1602565: p = 7.73e-05, odds ratio = 1.11. Our results provide a comprehensive and up-to-date review of candidate gene association studies in schizophrenia. Findings complement results from GWASs in schizophrenia but also expand the current list of candidate loci for schizophrenia.
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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 | 0.015 | 0.035 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.012 | 0.043 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 0.001 |
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".