Accelerated transcriptomic age and susceptibility to traffic-related air pollution among cardiac catheterization patients
Background: Accelerated transcriptomic and/or epigenetic age have been proposed as biomarkers of disrupted systemic health and may contribute to increased sensitivity to environmental exposures. Previously, we have observed that epigenetic age acceleration may be a biomarker of sensitivity to air pollution, especially for traffic-related air pollution (TRAP) in urban cohorts.
Methods: Using 1,024 participants from the CATHGEN cohort, we evaluated whether accelerated transcriptomic aging increases cardiovascular sensitivity to TRAP exposure. We used residential proximity to major roadways as a measure of TRAP exposure and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used gene expression-based age acceleration (GEXAge AAD) and Horvath epigenetic age acceleration (DNAmAge AAD) from blood as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, socioeconomic status, body mass index, hyperlipidemia, and diabetes. Linear regression models were used for blood pressure outcomes and logistic regression for PAD. Differences in associations by aging biomarkers were examined using both stratified models (median) and multiplicative interaction models.
Results: We observed significant interactions between TRAP and both median-stratified GEXAge AAD and DNAmAge AAD, but these interactions were notably weaker than in previous analyses that only included urban communities. Constraining the cohort to those residing in more urban environments further strengthened the interaction between GEXAge AAD and TRAP. Interactions indicated that increased transcriptomic or epigenetic age acceleration elevated associations between proximity to roadways and PAD, with the strongest interactions identified for those with both accelerated epigenetic and transcriptomic age.
Conclusion: Similar to epigenetic age, elevated transcriptomic age may also be an indicator of increased sensitivity to TRAP exposure. Individuals with jointly elevated epigenetic and transcriptomic age may have even greater environmental health risks than those with just elevated transcriptomic age.