Ancestry-Calibrated Polygenic Risk Scores Predict PTSD Trajectories in Recent Trauma Survivors and Interact with...

Area of Science:

• Genetics
• Psychiatry
• Environmental Health

Background:

• Polygenic risk scores (PRS) for PTSD often explain limited variance and face challenges in cross-group comparisons due to ancestry-related differences.
• Gene-by-environment (GxE) analyses for PTSD are complicated by inequitable distribution of socioenvironmental exposures across ethnoracial groups.

Purpose of the Study:

• To construct an ancestry-calibrated polygenic risk score (AC-PRS) for PTSD.
• To investigate GxE interactions using AC-PRS in a large longitudinal study of trauma survivors.

Main Methods:

• Developed an AC-PRS for PTSD in 1,801 trauma survivors.
• Analyzed six PTSD trajectories identified from PCL-5 scores over six months.
• Examined interactions between AC-PRS and neighborhood factors (NDVI, ADI) using logistic and linear regression models.

Main Results:

• AC-PRS explained significant variability (R²=.053) in PTSD trajectories across ethnoracial groups.
• Area deprivation index (ADI) moderated the association between AC-PRS and high nonremitting PTSD trajectories and symptom severity at six months.
• No significant interactions were found between NDVI and AC-PRS.

Conclusions:

• AC-PRS effectively captures PTSD genetic risk in admixed trauma survivors, distinguishing between nonremitting and resilient PTSD courses.
• Neighborhood disadvantage may alter the utility of PRS for PTSD, necessitating careful contextual application.