19 Aug Genes Responsible For Cardiometabolic Diseases Identified
MedicalResearch.com Interview with:
Johan LM Björkegren, MD, PhD
Professor, Chief Clinical Science Officer
Department of Genetics and Genomic Sciences
Icahn Institute for Genomics and Multiscale Biology
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study was launched in 2007 by myself and Dr. Arno Ruusalepp MD, PhD, Chief Cardiac Surgeon at Tartu University Hospital in Estonia, and senior co-author on the study. Unlike similar studies, STARNET obtained samples of several key tissues from 600 clinically well-characterized patients with CAD during coronary artery bypass surgery. By using sophisticated data analysis techniques, the researchers found that the gene expression data from STARNET were highly informative in identifying causal disease genes and their activity in networks not only in CAD but also for other cardiometabolic diseases as well as Alzheimer’s disease.
By analyzing gene-expression data from multiple tissues in hundreds of patients with coronary artery disease, we were able to identify disease-causing genes that either were specific to single tissues or acted across multiple tissues in networks to cause cardiometabolic diseases.
MedicalResearch.com: What should readers take away from your report?
Response: The STARNET study is to date the by far largest data-driven study offering mechanisms for the hundreds, even thousand of DNA risk markers that have been associated with cardiovascular diseases by previous genetic studies (so called “genome-wide association studies” or “GWAS”). Identifying disease-causal genes with target tissue/organ, as we have started to do with STARNET, is a prerequisite to develop precision medicine with individualized diagnostics and therapies tailored to each patient.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The STARNET study brings several more or less unexpected results. One is that fat, particular abdominal fat emerges as largely overviewed target tissue to control blood lipid levels such LDL (“bad”)cholesterol. Another one is that disease-casual genes are highly shared across tissues and cardiometabolic diseases as well as Alzheimer’s Disease. Overall, the STARNET study sends the message that we now need more of disease-focused genetics of gene (RNA) expression studies also outside coronary artery disease.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
O. Franzen, R. Ermel, A. Cohain, N. K. Akers, A. Di Narzo, H. A. Talukdar, H. Foroughi-Asl, C. Giambartolomei, J. F. Fullard, K. Sukhavasi, S. Koks, L.-M. Gan, C. Giannarelli, J. C. Kovacic, C. Betsholtz, B. Losic, T. Michoel, K. Hao, P. Roussos, J. Skogsberg, A. Ruusalepp, E. E. Schadt, J. L. M. Bjorkegren. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases. Science, 2016; 353 (6301): 827 DOI: 10.1126/science.aad6970
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