Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data
Bibliographic record
Abstract
Abstract Genome-wide association studies (GWAS) of suicidal thoughts and behaviors support the existence of genetic contributions. Continuous measures of psychiatric disorder symptom severity can sometimes model polygenic risk better than binarized definitions. We compared two severity measures of suicidal thoughts and behaviors at the molecular and functional levels using genome-wide data. We used summary association data from GWAS of four traits analyzed in 122,935 individuals of European ancestry: thought life was not worth living (TLNWL), thoughts of self-harm , actual self-harm , and attempted suicide . A new trait for suicidal thoughts and behaviors was constructed first, phenotypically, by aggregating the previous four traits (termed “suicidality”) and second, genetically, by using genomic structural equation modeling (gSEM; termed S-factor). Suicidality and S-factor were compared using SNP-heritability ( h 2 ) estimates, genetic correlation ( r g ), partitioned h 2 , effect size distribution, transcriptomic correlations ( ρ GE ) in the brain, and cross-population polygenic scoring (PGS). The S-factor had good model fit ( χ 2 = 0.21, AIC = 16.21, CFI = 1.00, SRMR = 0.024). Suicidality ( h 2 = 7.6%) had higher h 2 than the S-factor ( h 2 = 2.54, P diff = 4.78 × 10 −13 ). Although the S-factor had a larger number of non-null susceptibility loci (π c = 0.010), these loci had small effect sizes compared to those influencing suicidality (π c = 0.005, P diff = 0.045). The h 2 of both traits was enriched for conserved biological pathways. The r g and ρ GE support highly overlapping genetic and transcriptomic features between suicidality and the S-factor. PGS using European-ancestry SNP effect sizes strongly associated with TLNWL in Admixed Americans: Nagelkerke’s R 2 = 8.56%, P = 0.009 (PGS suicidality ) and Nagelkerke’s R 2 = 7.48%, P = 0.045 (PGS S-factor ). An aggregate suicidality phenotype was statistically more heritable than the S-factor across all analyses and may be more informative for future genetic study designs interested in common genetic factors among different suicide related phenotypes.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".