Polygenic risk associated with post-traumatic stress disorder onset and severity
Abstract
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 R2 = 4.68%, P = 0.003) and severity (R2 = 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 R2 = 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 07, 2019
- Source ID
- 10.1038/s41398-019-0497-3
Entities
People
- Aarti Gautam
- Adriana Lori
- Bernie J. Daigle Jr.
- Burook Misganaw
- Charles R. Marmar
- Duna Abu-amara
- Francis J. Doyle III
- Guia Guffanti
- Inyoul Lee
- Janine D. Flory
- Kai Wang
- Kerry J. Ressler
- Leroy Hood
- Marti Jett
- Owen M. Wolkowitz
- Rachel Yehuda
- Rasha Hammamieh
- Ruoting Yang
- Sbpbc
- Susanne G Mueller
- Synthia H Mellon
Organizations
- Armed Forces Institute of Regenerative Medicine
- Telemedicine and Advanced Technology Research Center
- United States Army Medical Research and Development Command