Genomic profiling of human vascular cells identifies < i > TWIST1 < /i > as a causal gene for common vascular diseases

by Sylvia T. Nurnberg, Marie A. Guerraty, Robert C. Wirka, H. Shanker Rao, Milos Pjanic, Scott Norton, Felipe Serrano, Ljubica Perisic, Susannah Elwyn, John Pluta, Wei Zhao, Stephanie Testa, YoSon Park, Trieu Nguyen, Yi-An Ko, Ting Wang, Ulf Hedin, Sanjay Sinha, Yoseph Barash, Christopher D. Brown, Thomas Quertermous, Daniel J. Rader Genome-wide association studies have identified multiple novel genomic loci associated with vascular diseases. Many of these loci are common non-coding variants that affect the expression of disease-relevant genes within coronary vascular cells. To identify such genes on a genome-wide level, we pe rformed deep transcriptomic analysis of genotyped primary human coronary artery smooth muscle cells (HCASMCs) and coronary endothelial cells (HCAECs) from the same subjects, including splicing Quantitative Trait Loci (sQTL), allele-specific expression (ASE), and colocalization analyses. We identifie d sQTLs forTARS2,YAP1,CFDP1, andSTAT6 in HCASMCs and HCAECs, and 233 ASE genes, a subset of which are also GTEx eGenes in arterial tissues. Colocalization of GWAS association signals for coronary artery disease (CAD), migraine, stroke and abdominal aortic aneurysm with GTEx eGenes in aorta, coronary artery and tibial artery discovered novel candidate risk genes for these diseases. At the CAD and stroke locus tagged by rs2107595 we demonstrate colocalization with expression of the proximal geneTWIST1. We show that disrupting the rs2107595 locus altersTWIST1 ...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research