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INTRODUCTION: Most of previous studies have examined effects of acute psychological stress in humans on selected panels of genes. The genomic approach may help identify novel genes that underline biological mechanisms of acute psychological stress responses. OBJECTIVE: This exploratory study aimed to investigate genome-wide transcriptional activity changes in response to acute psychological stress. METHODS: The sample included 40 healthy women (mean age 31±11.6 years). Twenty-two participants had a stress experience induced by the Trier Social Stress Test (TSST) (experimental group) and 18 did not (control group). Psychological stress levels and hemodynamic changes were assessed before and after the TSST. The peripheral blood samples obtained before and after the TSST were processed for mRNA-sequencing. RESULTS: The psychological and hemodynamic stress parameters indicated that the TSST induced moderate levels of stress in the experimental group. Six genes (HCG26, HCP5, HLA-F, HLA-F-AS1, LOC1019287, and SLC22A16) were up-regulated, and five genes (CA1, FBXO9, SNCA, STRADB, and TRMT12) were down-regulated, among those who experienced the stress induction, compared with the control group. Nine genes out of 11 were found in the network of endocrine system disorders, neurological disease, and organismal injury and abnormalities. CONCLUSION: The identified genes such as HCP5, SLC22A16, and SNCA have previously been proposed as the therapeutic targets of cancer and Parkinson’s disease. Future studies are suggested to examine pathological mechanisms by which the identified genes may mediate the association between psychological stress and adverse health outcomes. Such studies may ultimately identify therapeutic targets that enhance biological resilience to the adverse effects of psychological stress.

Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary arteries and 19% exhibited cell-type-specific expression. Colocalization analysis with GWAS identified subgroups of eGenes unique to CAD and blood pressure. Fine-mapping highlighted additional eGenes of interest, including TBX20 and IL5 . Splicing (s)QTLs for 1,690 genes were also identified, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing events to accurately identify disease-relevant gene expression. Our work provides the first human coronary artery eQTL resource from a patient sample and exemplifies the necessity of diverse study populations and multi-omic approaches to characterize gene regulation in critical disease processes.