Publications

Resilience to stress integrates cognitive, physiological, and behavioral adaptations to sustain performance under adversity. Genetic variation in catechol-O-methyltransferase (COMT, rs4680) and angiotensin-converting enzyme (ACE, rs1799752) modulates dopaminergic and renin–angiotensin signaling, influencing tissue oxygenation and fatigue resistance.

We examined COMT- and ACE-promoter methylation and genotypes in relation to resilience traits in Swiss tactical athletes (24.6 years) with a maximal power output of 534 W and 21,656 W, respectively, during cardiopulmonary exercise and elbow strike testing.

At a 5% false-discovery rate, COMT genotype/methylation explained ~12% of the variance in cognitive performance and metabolic resilience, while ACE explained ~6–7% in strength-endurance and muscle resistance. Antidromic linear associations between COMT genotype and methylation with visual reaction time under reactive stress indicate opposing regulatory influences, best captured by regression models incorporating (epi)genetic covariates. The strongest methylation effects involved COMT promoter associations with muscle hemoglobin content across cardiopulmonary exercise zones (r = 0.43–0.58) and sport-specific strain (r = −0.46). COMT- and ACE-promoter methylation, correlated with time spent in the first aerobic training zone (r = 0.55 and 0.32), indicating environmentally responsive epigenetic modulation.

These findings highlight neurovascular–metabolic coupling via dopaminergic and renin–angiotensin pathways as a key mechanism in stress adaptation. System-level adaptations in these pathways align with COMT and ACE (epi)genetic blood profiles, positioning them as candidate resilience biomarkers. Larger, preregistered studies with site-specific CpG analyses and mechanistic assays are needed to establish causal relevance and translational utility for resilience-informed performance optimization in high-stakes professionals.

Keywords: biomarker, cardiopulmonary, near-infrared spectroscopy, tensiomyography, exercise, soldier, genetic, physical activity, training, performance, cognition

In the studied cohort of Swiss tactical athletes, COMT and ACE exhibit distinct (epi)genetic associations with resilience-related cognitive and physiological traits. Promoter methylation of COMT correlates with cognitive performance under stress and oxygen utilization metrics, whereas ACE-promoter methylation is associated with strength–endurance and muscle oxygenation. Antidromic patterns between COMT genotype and methylation suggest complex regulatory dynamics. Observed methylation levels appear sensitive to recent training exposure and perceived strain, potentially reflecting adaptive, environment-responsive signaling.

While these (epi)genetic factors contribute modestly to interindividual variability in performance, these data support a biologically plausible neurovascular link involving ACE- and COMT-gene activity-regulated catecholaminergic and angiotensin pathways. The findings align with the hypothesis that ACE- and COMT-gene-related profiles may inform personalized conditioning strategies; however, causal inference remains limited due to the observational nature and cohort size of this study. To substantiate the eventual prognostic robustness of identified relationships, exploring site-specific methylation effects and elucidating the underlying (regulatory) mechanisms, larger, longitudinal studies in genetically homogeneous populations is warranted.