Abstract 1877: The Transcriptome of Monocytes as a Multidimensional Cardiovascular Biomarker
A growing interest has focused on the “genetics of gene expression” with the possibility of conducting large scale studies linking genome-wide variability to genome-wide expression. Investigating the sources of variability of the transcriptome may reveal patterns of gene expression that reflect disease predisposition. In a large population-based cohort (N=1,490), we have analyzed 12,808 genes expressed in circulating monocytes - a key cell for atherosclerosis and immunity, in relation to genome-wide variability (characterized by single nucleotide polymorphisms (SNPs), N=675,350 SNPs) and cardiovascular risk factors. Our results show that approximately 20% of the genes were significantly associated with SNPs that modulate expression of these genes in cis. Further, age, gender, body mass index, cigarette smoking and plasma C-reactive protein were strong modulators of expression whereas lipids, glycemia and blood pressure had little influence on monocytes expression. Expression traits influenced by risk factors were more likely to be genetically regulated, suggesting that some genes are particularly responsive to any type of influence. Among them, a subset of genes was of particular relevance for atherosclerosis as it connects lipid metabolism, immunity and inflammation. This study demonstrates that the monocyte transcriptome represents a sophisticated multidimensional integrator of genetic and non-genetic influences which may inform on ongoing pathophysiological processes.