Investigation of correlations between DNA methylation, suicidal behavior and aging
Bibliographic record
Abstract
Objectives Suicidal behavior ( SB ) is a major cause of mortality for patients diagnosed with bipolar disorder ( BD ). In this study, we investigated epigenetic differences in BD participants with and without a history of SB . Methods We used suicidality scores constructed from Schedule for Clinical Assessments in Neuropsychiatry ( SCAN ) interview questions about suicidal thought and behavior to identify individuals from a BD cohort of n=452; participants with the most extreme high (H‐ SB , n=18) and most extreme low (L‐ SB , n=22) scores were used as cases and controls, respectively. Epigenome‐wide DNA methylation patterns were compared between the two groups using the Illumina Infinium Human Methylation 450 BeadChip microarray. DNA methylation age was compared to chronological tissue age. Results We observed highly significant differences in methylation between cases and controls in three genomic regions enriched for epigenetic modifications corresponding to gene regulatory regions. BD participants with a history of SB showed less overall methylation in the 5′ untranslated region of Membrane palmitoylated protein 4 ( MPP 4 ) ( P =7.42×10 −7 ) and in intron 3 of TRE2/BUB2/CDC16 domain family member 16 ( TBC 1D16 ) ( P =6.47×10 −7 ), while exon 1 of Nucleoporin 133 ( NUP 133 ) was less methylated in controls ( P =1.17x10 ‐6 ). Moreover, we observed a greater correlation between DNA methylation age and tissue age in controls ( r =.91, P <.0001) than in the H‐ SB group ( r =.83, P <.0001). Conclusions We report significant findings at three loci based on a methylome scan of participants with BD for an SB phenotype, and potentially altered molecular aging in suicide attempters. Despite the small sample size, our proof‐of‐concept study highlights the potential for epigenetic factors to be useful in understanding the molecular underpinnings of suicide with the ultimate aim of its prevention.
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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 | 0.000 | 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 | 0.000 | 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".