Chromatin Capture Identifies SCARB1-LAG3 Proinflammatory Cardiovascular Disease Gene Networks [Hi-C]

Purpose: Utilized Next-generation sequencing (NGS) to profile global chromatin interaction differences between two populations, a selected carrier (C) alele of SNP (rs10846744) associated with cardiovascular disease (CVD) and a selected non-carrier (G) allele. Methods: Chromatin was isolated from two subjects, one homozygous for the rs10846744 reference (G) allele and one homozygous for the rs10846744 risk (C) allele, processed for dilution HiC (Lieberman-Aiden, van Berkum et al., 2009) and then subjected next-gen sequencing. Results: HiC-Pro integrated pipeline (with default parameters) was used for generating the HiC contact probability matrices (Servant et al., 2015). The results were visualized using HiCPlotter (Akdemir and Chin, 2015) and HiTC (Servant et al., 2012) and the Washington University EpiGenome Browser (Zhou and Wang, 2013). Juicebox (Durand et al., 2016) was utilized to extract observed/expected KR (Knight-Ruiz) normalized contacts for chromosome 12. Conclusions: Our study represents the first detailed analysis of significant changes in gene expression by an altered chromatin interaction network from SCARB1 to NR2F2 and LAG3, contributing to CAD proinflammatory gene networks. Overall design: Reference (GG) was compared to Risk (CC)