A genome-wide association study of outcome from traumatic brain injury

Kals, Mart; Kunzmann, Kevin; Parodi, Livia; Radmanesh, Farid; Wilson, Lindsay; Izzy, Saef; Anderson, Christopher; Puccio, Ava M.; Okonkwo, David O.; Temkin, Nancy; Stein, Murray B.; Manley, Geoff; Maas, Andrew I.R.; Richardson, Sylvia; Palotie, Aarno; Ripatti, Samuli; Rosand, Jonathan; Menon, David

doi:10.1016/j.ebiom.2022.103933

Cited by 30 publications

(13 citation statements)

References 55 publications

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“…A previous study also showed that APOE ε4 does not have a significant effect on the prognosis of TBI patients. 17 This differs from the results of the present study. This may be because our study had a small sample size and was a single‐center clinical study with statistical limitations.…”

Section: Resultscontrasting

confidence: 99%

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury

Lin

Li²,

Sun

et al. 2023

Ann Clin Transl Neurol

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Objective To investigate the effects of the apolipoprotein E (APOE) gene on oxygen saturation and cerebral perfusion in the early stages of traumatic brain injury (TBI). Methods This study included 136 consecutive TBI patients and 51 healthy individuals. The APOE genotypes of all subjects were determined using quantitative fluorescence polymerase chain reaction (QF‐PCR). Regional cerebral oxygen saturation (rScO2) of patients with TBI and normal subjects was monitored using near‐infrared spectroscopy (NIRS). Computed tomography (CT) perfusion was used to obtain cerebral perfusion in patients with TBI and normal subjects. Results In the TBI group, the rScO2 of APOEε4 carriers (53.06 ± 6.87%) was significantly lower than that of non‐carriers (58.19 ± 5.83%, p < 0.05). Meanwhile, the MTT of APOEε4 carriers (6.75 ± 1.30 s) was significantly longer than that of non‐carriers (5.87 ± 1.00 s, p < 0.05). Furthermore, correlation analysis showed a negative correlation between rSCO2 and MTT in patients with TBI. Both the univariate and multifactorial logistic regression analyses revealed that APOE ε4, hypoxia, MTT >5.75 s, Marshall CT Class, and GCS were independent risk factors for early poor prognosis in patients with TBI. Conclusion Both cerebral perfusion and cerebral oxygen were significantly impaired after TBI, and low cerebral perfusion and hypoxia were related to poor prognosis of patients with TBI. Compared with APOE ε4 non‐carriers, APOE ε4 carriers not only had poorer cerebral perfusion and cerebral oxygen metabolism but also worse prognosis in the early stages of TBI. Furthermore, a negative correlation was observed between the rSCO2 and MTT levels. In addition, both CT perfusion scanning (CTP) and NIRS are reliable for monitoring the condition of patients with TBI in the neurological intensive care unit (NICU).

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Section: Resultscontrasting

confidence: 99%

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury

Lin

Li²,

Sun

et al. 2023

Ann Clin Transl Neurol

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“…Recovery after mTBI varies among the patient population with some patients displaying better outcome measures than others. These differences in outcomes may be attributed to pre-existing conditions, genetic factors or concurrent polytrauma [ 36 , 74 ]. However, less attention has been paid to the effect of secondary insults during the chronic phase of mTBI on outcome measures, and the consequences are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Impact of gulf war toxic exposures after mild traumatic brain injury

Ferguson

McCartan

Browning

et al. 2022

acta neuropathol commun

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Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery.

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“…The methods for DNA collection, genotyping, imputation, quality control, and ancestry assignment are reported in a previous publication [ 24 ]. Genotyping of the TRACK-TBI individuals was conducted at the Broad Institute of MIT and Harvard, using the Illumina Global Screening Array (GSA-24v2–0 + Multi-Disease).…”

Section: Participants and Methodsmentioning

confidence: 99%

Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury

et al. 2023

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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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A genome-wide association study of outcome from traumatic brain injury

Cited by 30 publications

References 55 publications

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury

Impact of gulf war toxic exposures after mild traumatic brain injury

Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury

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