Abstract Body: Background: A healthy diet is crucial for preventing cardiovascular disease (CVD) by modulating gene expression, but the gene pathways remain poorly studied.
Hypothesis: Healthy dietary intake is associated with a favorable blood transcriptomic profile, which in turn is associated with a lower CVD risk.
Methods: Among HCHS/SOL participants with dietary and transcriptome data (n = 6796), we performed cross-sectional analyses to identify whole-blood RNA sequencing (RNA-seq) signatures of a healthy dietary pattern assessed by Alternative Healthy Eating Index (AHEI), where higher scores indicate a healthier diet. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to characterize diet-related gene modules and examined their associations with incident CVD.
Results: Out of 18989 RNA-seq features, we identified 375 RNA-seq signatures associated with AHEI (FDR-q <0.10; Fig. A). These identified RNA-seq signatures were clustered into four co-expressed gene modules (Fig. B), including an adaptive immunity module and an innate immunity & oxidative stress module involving IL-17 and NF-κB signaling (Fig. C). The adaptive immunity module was positively associated with AHEI and with blood immune traits reflecting adaptive immune activation (e.g., higher proportions of activated CD4+ and CD8+ T lymphocytes). By contrast, the innate immunity & oxidative stress module was negatively associated with AHEI and positively with traits indicative of innate immune activation (e.g., higher neutrophil proportions; Fig. D). Furthermore, higher levels of adaptive immunity module were associated with a lower CVD risk (HR [95% CI]: 0.84 [0.72–0.98]), whereas higher levels of innate immunity & oxidative stress module were associated with a higher CVD risk (1.19 [1.02–1.39]; Fig. E).
Conclusions: Adherence to a healthy dietary pattern is associated with a favorable blood transcriptomic profile related to adaptive and innate immune pathways, which may help explain the protective association between healthy diet and CVD.