Ancestry-Calibrated Polygenic Risk Scores Predict PTSD Trajectories in Recent Trauma Survivors and Interact with Neighborhood Resources
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Objective: Polygenic risk scores (PRS) for posttraumatic stress disorder (PTSD) often account for a low amount of variance. Ancestry-related differences in PRS scale and variance limit cross-group comparisons. This methodological challenge further complicates gene-by-environment (GxE) analyses, given that socioenvironmental exposures are inequitably distributed across ethnoracial groups. We constructed an ancestry-calibrated polygenic risk score (AC-PRS) for PTSD in the largest longitudinal study of trauma survivors to date and investigated GxE interactions. Method: Recent trauma survivors (N=1,801) provided a blood specimen for genotyping. Six PTSD trajectories were previously identified from PTSD Checklist for DSM-5 (PCL-5) scores at 2-weeks, 8-weeks, 3-months, and 6-months post-trauma. Greenspace (normalized difference vegetation index [NDVI) and socioeconomic disadvantage (area deprivation index [ADI]) were derived from residential addresses. Logistic regressions examined interactions between newly developed AC-PRS and neighborhood factors on trajectories after adjusting for sociodemographic and trauma-related covariates. Secondary linear models considered GxE interactions on 6-month PCL-5 scores. Results: < .05). There were no NDVI x AC-PRS interactions in any models. Conclusions: AC-PRS captures genetic risk for PTSD in admixed trauma survivors, demonstrating good discrimination between nonremitting and resilient courses of PTSD. However, neighborhood disadvantage may modify utility of PRS for PTSD, warranting careful consideration when applying these scores across contexts.
Source: medRxiv
Authors: E. Kate Webb, Aarti Jajoo, Vijetha Balakundi, Mohammad S.E. Sendi, Karestan C. Koenen, Sarah D. Linnstaedt, Stacey L. House, Xinming An, Jennifer S. Stevens, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Claire Pearson, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O’Neil, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Ronald C. Kessler, Samuel A. McLean, Kerry J. Ressler, Nikolaos P. Daskalakis, Nathaniel G. Harnett
Institutions: Harvard University, Duke University, McLean Hospital, Duke Medical Center, Broad Institute, Stanley Center for Psychiatric Research, Boston University, Georgia Institute of Technology, Emory University, Georgia State University, Center for Translational Research in Neuroimaging and Data Science, University of North Carolina at Chapel Hill, Washington University in St. Louis, University of California, San Francisco, Wayne State University, University of Massachusetts Chan Medical School, Vanderbilt University Medical Center, Henry Ford Health, Indiana University Indianapolis, Indiana University School of Medicine, University of Florida, University of Florida Health Science Center, Cooper Medical School of Rowan University, The Ohio State University, University of Pennsylvania, Thomas Jefferson University, Thomas Jefferson University Hospital, Jefferson Einstein Philadelphia Hospital, Brigham and Women's Hospital, Trinity Health Ann Arbor Hospital, Baystate Medical Center, Detroit Receiving Hospital, The University of Texas Health Science Center at Houston, University of Missouri–St. Louis, University of Michigan, Michigan Medicine
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
Awards: Training Program in Psychiatric Genetics and Translational Research, A Multidimensional Neuroimaging Investigation of Posttraumatic Stress in Humans, Longitudinal Assessment of Post-traumatic Syndromes, Psychiatric Genomics Consortium for PTSD, Extracellular vesicles as biomarkers of trauma exposure and PTSD risk, Mobile Measures of Threat Sensitivity for Cross-sectional and Longitudinal Assessment, Training to Enhance Alignment of Psychiatry and Neuroscience, Next steps for PTSD genomics: from loci to function
OpenAlex ID: W7169798495