Coronary heart disease was associated with differential expression of 35 genes (false discovery rate <0.5), including clusters linked to increased erythrocyte production and reduced T cell activity.
Case-Control (n=376)
Transcriptomic profiling identified specific gene expression signatures associated with coronary heart disease, suggesting roles for altered hematopoiesis and disrupted innate immune activity.
p-value: p=FDR <0.5
OBJECTIVE: To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age- and sex-matched controls who were participants in the Framingham Heart Study. APPROACH AND RESULTS: A total of 35 genes were differentially expressed in cases with CHD versus controls at false discovery rate<0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene clusters associated with CHD, 2 linked to increased erythrocyte production and a third to reduced natural killer and T cell activity in cases with CHD. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and T-cell-related pathways with CHD. CONCLUSIONS: Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention.
Joehanes et al. (Fri,) conducted a case-control in Coronary Heart Disease (n=376). Coronary heart disease vs. Age- and sex-matched controls was evaluated on Differentially expressed genes (p=FDR <0.5). Coronary heart disease was associated with differential expression of 35 genes (false discovery rate <0.5), including clusters linked to increased erythrocyte production and reduced T cell activity.