International team IDs genes determining risk for cardiometabolic disease

DNA

A group of scientists has unlocked the interaction between genes in certain tissues that can play a role in the hereditary risk for cardiometabolic diseases, including conditions that can lead to heart attack and stroke.

Initially looking at coronary artery disease patients, Mount Sinai researchers collaborated with colleagues from AstraZeneca, Tartu University Hospital in Estonia, the Karolinska Institutet and the Science for Life Laboratory in Sweden to systematically analyze RNA sequence data, according to a statement. They looked at 600 CAD patients’ RNA sequence data from blood, vascular and metabolic tissues. These sequences act as a blueprint for DNA protein synthesis, governing whether a particular tissue stays healthy or becomes diseased. Despite the early focus on CAD, they found that disease-causing genes transcended tissue type and 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,” said Dr. Johan Björkegren, a senior author of the study and a professor of genetics and genomic sciences at Mount Sinai’s Icahn School of Medicine, in the statement. Cardiometabolic disease refers to a group of interrelated risk factors that can promote the onset of atherosclerotic vascular disease and Type 2 diabetes.

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This analysis, dubbed Starnet, built on previous genome-wide association studies, which identified thousands of DNA variants that elevated the risk for CAD. The new research pinpointed the genes affected by these variants as targets for new diagnostics and therapies, Björkegren said in the statement. Uncovering which tissues, pathways and molecular networks these disease genes affect, and how, will be a stepping stone in the development of individualized therapies and diagnostics, he said.

Björkegren’s team is already applying the research to drug development, along with AstraZeneca and the SciLifeLab. “During the course of our project we have found that Dr. Björkegren’s datasets including STARNET provide essential translation information to help us identify new drug targets, as well as informing on existing targets in cardiovascular and metabolic diseases, a main therapy area for AstraZeneca,” said Dr. Li-Ming Gan, a study co-author and senior medical director at AstraZeneca.

- here's the statement

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