Association between suicidal ideation and tandem repeats in contactins
Bibliographic record
Abstract
Background Death by suicide is one of the leading causes of death among adolescents. Genome-wide association studies (GWAS) have identified loci that associate with suicidal ideation and related behaviours. One such group of loci are the six contactin genes (CNTN1-6) that are critical to neurodevelopment through regulating neurite structure. Because single nucleotide polymorphisms (SNPs) detected by GWAS often map to non-coding intergenic regions, we investigated whether repetitive variants in CNTNs associated with suicidality in a young cohort aged 8 to 21. Understanding the genetic liability of suicidal thought and behavior in this age group will promote early intervention and treatment. Methods Genotypic and phenotypic data were obtained from the Philadelphia Neurodevelopment Cohort (PNC). Across six CNTNs, 232 short tandem repeats (STRs) were analyzed in up to 4,595 individuals of European ancestry who expressed current, previous, or no suicidal ideation. STRs were imputed into SNP arrays using a phased SNP-STR haplotype reference panel from the 1000 Genomes Project. We tested several additive and interactive models of locus-level burden (i.e., sum of STR alleles) with respect to suicidal ideation. Additive models included sex, birth year, developmental stage (“DevStage”), and the first 10 principal components of ancestry as covariates; interactive models assessed the effect of STR-by-DevStage considering all other covariates. Results CNTN1-[T]N interacted with DevStage to increase risk for current suicidal ideation (CNTN1-[T]N-by-DevStage; p = 0.00035). Compared to the youngest age group, the middle (OR = 1.80, p = 0.0514) and oldest (OR = 3.82, p = 0.0002) participant groups had significantly higher odds of suicidal ideation as their STR length expanded; this result was independent of polygenic scores for suicidal ideation. Discussion These findings highlight diversity in the genetic effects (i.e., SNP and STR) acting on suicidal thoughts and behavior and advance our understanding of suicidal ideation across childhood and adolescence.
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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 | 0.001 | 0.003 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".