Polygenic risk associated with post-traumatic stress disorder onset and severity.
- Authors
- Misganaw, Burook; Guffanti, Guia; Lori, Adriana; Abu-Amara, Duna; Flory, Janine D; SBPBC; Mueller, Susanne; Yehuda, Rachel; Jett, Marti; Marmar, Charles R; Ressler, Kerry J; Doyle, Francis J
- Year
- 2019
- Journal
- Translational psychiatry
- PMID
- 31175274
- DOI
- 10.1038/s41398-019-0497-3
- PMCID
- PMC6555815
Post-traumatic stress disorder (PTSD) is a psychiatric illness with a highly polygenic architecture without large effect-size common single-nucleotide polymorphisms (SNPs). Thus, to capture a substantial portion of the genetic contribution, effects from many variants need to be aggregated. We investigated various aspects of one such approach that has been successfully applied to many traits, polygenic risk score (PRS) for PTSD. Theoretical analyses indicate the potential prediction ability of PRS. We used the latest summary statistics from the largest published genome-wide association study (GWAS) conducted by Psychiatric Genomics Consortium for PTSD (PGC-PTSD). We found that the PRS constructed for a cohort comprising veterans of recent wars (n = 244) explains a considerable proportion of PTSD onset (Nagelkerke R = 4.68%, P = 0.003) and severity (R = 4.35%, P = 0.0008) variances. However, the performance on an African ancestry sub-cohort was minimal. A PRS constructed with schizophrenia GWAS also explained a significant fraction of PTSD diagnosis variance (Nagelkerke R = 2.96%, P = 0.0175), confirming previously reported genetic correlation between the two psychiatric ailments. Overall, these findings demonstrate the important role polygenic analyses of PTSD will play in risk prediction models as well as in elucidating the biology of the disorder.
Performance projections and upper bound of a genomic predictor for PTSD onset.Assuming 50,000 non-null contributing markers, coefficient of determination (fraction of variance explained) and corresponding AUC’s of genomic profiles built on finite number of samples are plotted in blue and red, respectively
PTSD onset and PTSD severity and stratification into risk groups with PRS.The first (lowest) quintile is used as a reference. For every other quintile, the mean difference in CAPS (or the odds ratio of PTSD onset) from the first quintile is plotted (corresponding to the dot in the plot). The bars indicate 95% confidence intervals around the mean differences (or odds ratios)
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|---|---|---|
| Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders. | 2023 | 37344610 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Polygenic Risk and Exposure Severity Predict Trajectories of PTSD: A Prospective Cohort Study. | Mann FD et al. | — | 2026 | → |
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