TY - JOUR
T1 - Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
AU - TRACK-TBI Investigators
AU - Stein, Murray B.
AU - Jain, Sonia
AU - Parodi, Livia
AU - Choi, Karmel W.
AU - Maihofer, Adam X.
AU - Nelson, Lindsay D.
AU - Mukherjee, Pratik
AU - Sun, Xiaoying
AU - He, Feng
AU - Okonkwo, David O.
AU - Giacino, Joseph T.
AU - Korley, Frederick K.
AU - Vassar, Mary J.
AU - Robertson, Claudia S.
AU - McCrea, Michael A.
AU - Temkin, Nancy
AU - Markowitz, Amy J.
AU - Diaz-Arrastia, Ramon
AU - Rosand, Jonathan
AU - Manley, Geoffrey T.
AU - Badjatia, Neeraj
AU - Duhaime, Ann Christine
AU - Ferguson, Adam R.
AU - Gopinath, Shankar
AU - Grandhi, Ramesh
AU - Madden, Christopher
AU - Merchant, Randall
AU - Schnyer, David
AU - Taylor, Sabrina R.
AU - Yue, John K.
AU - Zafonte, Ross
N1 - Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/12
Y1 - 2023/12
N2 - Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.
AB - Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.
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U2 - 10.1038/s41398-023-02313-9
DO - 10.1038/s41398-023-02313-9
M3 - Article
C2 - 36693822
AN - SCOPUS:85146843158
SN - 2158-3188
VL - 13
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 24
ER -