@article{a5bc38b6fe5f4d9785d6d608278ef258,
title = "Cross-Tissue Regulatory Gene Networks in Coronary Artery Disease",
abstract = "Summary Inferring molecular networks can reveal how genetic perturbations interact with environmental factors to cause common complex diseases. We analyzed genetic and gene expression data from seven tissues relevant to coronary artery disease (CAD) and identified regulatory gene networks (RGNs) and their key drivers. By integrating data from genome-wide association studies, we identified 30 CAD-causal RGNs interconnected in vascular and metabolic tissues, and we validated them with corresponding data from the Hybrid Mouse Diversity Panel. As proof of concept, by targeting the key drivers AIP, DRAP1, POLR2I, and PQBP1 in a cross-species-validated, arterial-wall RGN involving RNA-processing genes, we re-identified this RGN in THP-1 foam cells and independent data from CAD macrophages and carotid lesions. This characterization of the molecular landscape in CAD will help better define the regulation of CAD candidate genes identified by genome-wide association studies and is a first step toward achieving the goals of precision medicine.",
author = "Talukdar, {Husain A.} and {Foroughi Asl}, Hassan and Jain, {Rajeev K.} and Raili Ermel and Arno Ruusalepp and Oscar Franz{\'e}n and Kidd, {Brian A.} and Ben Readhead and Chiara Giannarelli and Kovacic, {Jason C.} and Torbj{\"o}rn Ivert and Dudley, {Joel T.} and Mete Civelek and Lusis, {Aldons J.} and Schadt, {Eric E.} and Josefin Skogsberg and Tom Michoel and Bj{\"o}rkegren, {Johan L.M.}",
note = "Funding Information: We thank Stephen Ordway for editorial assistance. This work was supported by the Swedish Heart-Lung Foundation (J.L.M.B. and J.S.), the Swedish Research Council (J.L.M.B. and J.S.), the King Gustaf V and Queen Victoria{\textquoteright}s Foundation of Freemasons (J.L.M.B. and J.S.), the Astra-Zeneca Translational Science Centre-Karolinska Institutet (J.L.M.B.), the University of Tartu (SP1GVARENG; J.L.M.B), the Estonian Research Council (ETF grant 8853; A.R. and J.L.M.B.), the Biotechnology and Biological Sciences Research Council (BBSRC, BB/J004235/1 and BB/M020053/1; T.M.), the American Heart Association (14SFRN20490315 and 14SFRN20840000; J.B. and E.E.S.), the NIH (National Heart, Lung, and Blood Institute [NHLBI], R01HL71207 [J.L.M.B.], K23HL111339 [C.G.], and K99HL121172 [M.C.]). Clinical Gene Networks AB (CGN) supported this work as a small and medium-sized enterprise (SME) of the EU FP6/FP7 project CVgenes@target (HEALTH-F2-2013-601456). This work was undertaken as part of the Leducq Consortium CAD Genomics (J.L.M.B., E.E.S., M.C., and A.J.L.). J.L.M.B., A.R., and T.M. are shareholders of CGN. J.L.M.B., E.E.S., and A.R. are members of the board of directors. CGN has an invested interest in the STAGE data. However, CGN has expressed no claims or sought any patents related to the results presented in this manuscript. Publisher Copyright: {\textcopyright} 2016 The Authors.",
year = "2016",
month = mar,
day = "23",
doi = "10.1016/j.cels.2016.02.002",
language = "English (US)",
volume = "2",
pages = "196--208",
journal = "Cell Systems",
issn = "2405-4712",
publisher = "Cell Press",
number = "3",
}