Clinical OMICS

JAN-FEB 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 24 of 51 January/February 2019 Clinical OMICs 23 kirstypargete / iStock / Getty Images risk of future heart events. The group used genetics, tran- scriptomics, epigenetics, and metabolomics to identify two ER stress genes (BRSK2 and HOOK2) that were differ- entially methylated in blood taken from more than 3,500 patients referred for cardiac catheterization as part of the CATHGEN study. "ER stress has long been linked to Type 1 diabetes and Parkinson's disease, among others, but this is the first indication that it is also playing a role in com- mon heart attacks and death from heart disease," Shah said at the time in a press release. Today, Shah and her colleagues have submitted several papers for publication that identify additional epigenetic biomarkers associated with cardiovascular disease. She said these studies have gotten even more precise in the last few years as the chips used to quantify methylation have gone from assessing 450,000 sites to including 850,000. "We use a lot of omics technology, not only to identify bio- markers, but to understand the biology of disease," Shah said. Using blood samples from patients and EPIC Bead- Chip technology to measure genome-wide methylation, the group has identified a transcription factor not previously implicated in heart disease. "Not only do we hope to be able to use methylation status of the transcription factor gene to predict whether a patient will have a heart attack in the next five years, but we also hope to better understand the biology of this transcription factor and maybe even find ways to regulate it." Psychiatry Few areas of medicine are more difficult than psychiatry when it comes to diagnosis, prognosis, and treatment. And, in terms of research, there are no tissues like tumors you can take from a live patient. Environment is known to play a significant role, and no two patients have the same presen- tation of disease. For these reasons, researchers working in psychiatry are hopeful epigenetic markers can shed light on the biology of these diseases and, ultimately, suggest drug targets. Dennis Grayson, Ph.D., is a professor of molec- ular neuroscience at the University of Illinois at Chicago. Grayson has studied the epigenetics of autism and alcohol- ism. In 2015, he was a part of a group that published a paper showing that adult mice whose mothers were exposed to restraint stress during pregnancy demonstrated behavioral abnormalities suggestive of schizophrenia. The brains of these mice had epigenetic signatures similar to those seen in the postmortem brains of patients with the disease. Using this mouse model, Grayson and colleagues are working to understand schizophrenia at the molecular level. It will be a long time before this work leads to clinical applications. Because of the heterogeneous nature of psychiatric disease symptoms, "you are going to have epigenetic complexity. Collectively, these changes contribute to the etiology of the disease. That's hampered our ability to identify clear biomarkers." Still, Grayson is optimistic, pointing out that methylation chips, next generation sequencing, and ATAC- Seq (see sidebar) are moving the basic research forward. In 2015, Kaminsky published a paper in Translational Psychiatry showing that DNA methylation and genetic variation of the SKA2 gene predicts suicidal behavior and post-traumatic stress. He agreed that the technol- ogy is there and the complexity of psychiatric disorders means that it will be some time before their clinical testing becomes a reality. For that, researchers will want a panel of 20 or so biomarkers, he said. "We have our promising suicide biomarker, and we need to see if it predicts risk. But, we are not doing that, yet. … We're looking for novel ways of finding new biomarkers, including using machine learning in analyses." Shah also said she sees the future of clinical epigenetics as panels of markers being tested and combined with other patient data to diagnose, treat, and manage disease. "That would be a systems biology approach and that would be ideal." Bodour Salhia, M.D., Keck School of Medicine, USC

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