Genetic susceptibility and risk of cardiometabolic diseases after traumatic brain injury
8 affiliations
- 1Division of Critical Care Neurology, Department of Neurology, Mass General Brigham
- 2Harvard Medical School
- 3Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- 4Cardiovascular Research Center, Massachusetts General Hospital
- 5Department of Biostatistics, Harvard T.H. Chan School of Public Health
- 6Department of Neurology, University of Pennsylvania Perelman School of Medicine
- 7Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine
- 8Division of Cardiology, Department of Medicine, Massachusetts General Hospital
Abstract
Background: Traumatic brain injury (TBI) has been linked to increased long-term cardiovascular and metabolic risk, but whether this reflects an independent effect of TBI or shared inherited susceptibility remains unclear. We aimed to (1) evaluate whether TBI is independently associated with incident coronary artery disease (CAD), hypertension (HTN), type 2 diabetes (DM2), and hypercholesterolemia (HLD); (2) test interactions between TBI and polygenic risk scores (PRS) on cardiometabolic outcomes; and (3) determine whether PRS improves risk prediction among TBI survivors beyond traditional clinical factors.
Methods: We performed two analyses in the UK Biobank. TBI was modeled as a time-varying exposure in Cox proportional hazards models to evaluate associations with incident cardiometabolic outcomes. Among participants with TBI, outcome-specific PRS were assessed for prediction beyond clinical covariates. A composite cardiometabolic meta-PRS was externally validated in the Mass General Brigham Biobank.
Results: Among 487,252 UK Biobank participants, 4,309 sustained incident TBI. TBI was independently associated with higher risk of CAD, HTN, DM2, and HLD. Joint TBI–PRS effects were largely additive. PRS was independently associated with each outcome among TBI survivors, most strongly for CAD and DM2. The meta-PRS was associated with greater post-TBI cardiometabolic risk in both UK Biobank (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.09–1.29) and the external replication cohort (HR, 1.15; 95% CI, 1.03–1.29).
Conclusion: TBI was independently associated with higher long-term cardiometabolic risk beyond traditional risk factors. Genetic susceptibility may further refine post-TBI risk stratification.
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BibTeX
@article{marini2026genetic,
title = {{Genetic susceptibility and risk of cardiometabolic diseases after traumatic brain injury}},
author = {Sandro Marini and Kelvin Supriami and Xingyu Chen and Zhiyu Yan and Carl Sadek and Anika Valluri and Roukoz Abou-Karam and Andrea L. C. Schneider and Stelios M. Smirnakis and Pradeep Natarajan and Saef Izzy and Akl C. Fahed},
journal = {Frontiers in Neurology},
year = {2026},
month = nov,
doi = {10.3389/fneur.2026.1975194},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1975194/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genetic susceptibility and risk of cardiometabolic diseases after traumatic brain injury
AU - Sandro Marini
AU - Kelvin Supriami
AU - Xingyu Chen
AU - Zhiyu Yan
AU - Carl Sadek
AU - Anika Valluri
AU - Roukoz Abou-Karam
AU - Andrea L. C. Schneider
AU - Stelios M. Smirnakis
AU - Pradeep Natarajan
AU - Saef Izzy
AU - Akl C. Fahed
PY - 2026
DA - 2026/11/09
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1975194
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1975194/full
AB - Background: Traumatic brain injury (TBI) has been linked to increased long-term cardiovascular and metabolic risk, but whether this reflects an independent effect of TBI or shared inherited susceptibility remains unclear. We aimed to (1) evaluate whether TBI is independently associated with incident coronary artery disease (CAD), hypertension (HTN), type 2 diabetes (DM2), and hypercholesterolemia (HLD); (2) test interactions between TBI and polygenic risk scores (PRS) on cardiometabolic outcomes; and (3) determine whether PRS improves risk prediction among TBI survivors beyond traditional clinical factors. Methods: We performed two analyses in the UK Biobank. TBI was modeled as a time-varying exposure in Cox proportional hazards models to evaluate associations with incident cardiometabolic outcomes. Among participants with TBI, outcome-specific PRS were assessed for prediction beyond clinical covariates. A composite cardiometabolic meta-PRS was externally validated in the Mass General Brigham Biobank. Results: Among 487,252 UK Biobank participants, 4,309 sustained incident TBI. TBI was independently associated with higher risk of CAD, HTN, DM2, and HLD. Joint TBI–PRS effects were largely additive. PRS was independently associated with each outcome among TBI survivors, most strongly for CAD and DM2. The meta-PRS was associated with greater post-TBI cardiometabolic risk in both UK Biobank (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.09–1.29) and the external replication cohort (HR, 1.15; 95% CI, 1.03–1.29). Conclusion: TBI was independently associated with higher long-term cardiometabolic risk beyond traditional risk factors. Genetic susceptibility may further refine post-TBI risk stratification.
SN - 1664-2295
ER -