Sex-stratified genomic structural equation models of posttraumatic stress inform PTSD etiology
Bibliographic record
Abstract
Posttraumatic stress disorder (PTSD) affects 3.9%-5.6% of the worldwide population, with well-documented sex-related differences. While psychosocial and hormonal factors affecting sex differences in PTSD and posttraumatic stress (PTS) symptom etiology have been explored, there has been limited focus on genetic bases of these differences. Many symptom combinations may confer a PTSD diagnosis. We hypothesized that these symptom combinations have sex-specific patterns, the examination of which could inform etiological differences in PTSD genetics between males and females. To investigate this, we performed a sex-stratified multivariate genome-wide association study (GWAS) in unrelated UK Biobank (UKB) individuals of European ancestry. Using GWAS summary association data, genomic structural equation modeling was performed to generate sex-specific factor models using six indicator variables: trouble concentrating, feeling distant from others, irritability, disturbing thoughts, upset feelings, and avoidance of places/activities which remind the individual of a traumatic event. Models of male and female PTSD symptoms differed substantially (local standardized root mean square difference=3.12) and significantly (χ 2 (5)=28.03, p=3.6x10 -5 ). Independent two-factor models best fit the data in both males and females; these factors were subjected to GWAS in each sex, revealing three genome-wide significant loci in females, mapping to SCAND3, WDPCP, and FAM120A. No genome-wide significant loci were identified in males. All four PTS factors (2 in males and 2 in females) were heritable (p<0.05): male PTS-f 1 h 2 -SNP=1.85%, male PTS-f 2 h 2 -SNP=1.47%, female PTS-f 1 h 2 -SNP=3.87%, female PTS-f 2 h 2 -SNP=3.53%. Male PTS-f 1 was enriched for medication-related putative causal relationships (3.73-fold, p=0.032) while male PTS-f 2 was enriched for body structure (2.84-fold, p=5.512x10 -7 ) and cognitive (3.22-fold, p=0.009) putative causal relationships. In females, PTS-f 1 was enriched for metabolic putative causal relationships (28.08-fold, p=0.035). By assessing the relationship between sex and PTSD symptoms, this study informs correlative and putatively causal etiological differences between males and females which support further investigation of sex differences in PTSD genetics.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.006 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".