Researchers discover DNA signatures linked to cardiovascular diseases

Recent research discovered DNA signatures linked to the risk for cardiovascular disease, a breakthrough that can lead to opportunities for clinical intervention years before the symptoms occur.

Cardiovascular Disease

Cardiovascular Disease. Image Credit: Billion Photos/Shutterstock.com

The study is based on analyses of data from five large heart cohort studies of diverse populations. The outcomes of the research have been published in the JAMA Cardiology journal.

The science is rapidly advancing in the area of epigenetics—modifications to our DNA that are often environmentally driven and have the potential to serve as an early warning sign for disease.”

Ana Navas-Acien, MD, PhD, Study First Author and Professor, Environmental Health Sciences, Columbia University Mailman School of Public Health

In this study, we harness the country’s best clinical data on heart disease from diverse populations to begin to unlock the specific epigenetic changes involved in the complex biology that leads to disease. Ultimately, we hope the research will allow us to identify and prevent disease before the worst damage takes place, although developing appropriate DNA methylation tests is still years away,” added Navas-Acien.

The scientists began their study with data from the Strong Heart Study, the largest cardiovascular disease study carried out in American Indians in collaboration with communities across the Great Plains and the Southwest since 1988.

They examined blood samples to pinpoint particular locations on DNA where methylation activity was linked to incidents of coronary heart disease, including heart attack and coronary deaths (methylation can alter the activity of a DNA segment without changing the genetic sequence).

The use of high-dimensional statistical methods allowed us to study methylation in hundreds of thousands of specific locations in the DNA at the same time.”

Arce Domingo-Relloso, MSc, Study Co-Author and Data Scientist, Columbia University Mailman School of Public Health

Arce Domingo-Relloso leads the statistical analyses for the research.

The scientists subsequently undertook the same method with four other major heart disease cohorts: Atherosclerosis Risk in Communities (divided into Black and white cohorts owing to differences in laboratory methods and timing), Framingham Heart Study, and Women’s Health Initiative. The researchers analyzed more than 400,000 DNA locations and 1,894 coronary heart disease events in total.

During the initial analysis of Strong Heart data, the researchers pinpointed 506 epigenetic marks associated with cardiovascular risk. Of these, 33 were associated with cardiovascular risk in three or more of the other cohorts. However, a few of these sites were linked with a higher risk of disease in one cohort but with a lower risk of disease in other cohorts.

Among the 33 methylation sites are sites linked previously to cardiovascular risk and smoking, along with new sites that the scientists anticipate of being worthy of future analyses. Further investigation of the similarities between the 33 marks showed that most of them are linked with the EGFR gene, involved in cell survival and cell growth.

The overlap of these methylation sites across diverse cohorts supports the idea of interconnected biological pathways for cardiovascular risk. The more we understand about the early risk for cardiovascular disease the better we may be able to prevent illness, particularly in populations such as American Indians with relatively high risk for heart disease.”

Yuling Hong, MD, PhD, Chief, Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute

Shelley A. Cole, Ph.D., from the Texas Biomedical Research Institute is the senior author of the study.

Source:
Journal reference:

Navas-Acien, A., et al. (2021) Blood DNA Methylation and Incident Coronary Heart Disease. JAMA Cardiology. doi.org/10.1001/jamacardio.2021.2704.

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