Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

Peripheral blood RNA-Seq from human coronary artery calcification cases and controls; Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. Eight cases and eight controls (matched for gender, age and ancestry); RNA sequencing of peripheral blood from a discovery set of eight CAC cases and eight matched controls was used to identify dysregulated genes, which were validated using the NanoString® and Affymetrix GeneChip® Human Exon ST Array platforms. The median CAC scores for cases in the screening and validation sets were 1531.5 and 668.5, respectively, while all controls had a score of zero.