November 25, 2020

Mental Health Post

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Preventive Healthcare Using Polygenic Risk Score for Coronary Artery Disease

Heart disease is the leading cause of death anywhere in the world and especially in India where it affects nearly 54.5 million people. A significant number of these deaths are in young people causing deaths due to heart attack in their 40’s and 50’s. Even the survivors must undergo expensivetreatment regimens and compromising on their productivity in the prime years of their lives. We have seen this happen a lot recently and there are several celebrities who have succumbed to heart attacks at a relatively young age lately. As it happens often by the time the signs and symptoms of heart disease show up it will probably be too late. What if there was a test that could tell you the risk of developing CAD much earlier in life, as early as possible.

Polygenic Risk Score (PRS) is one such concept that can tell the genetic risk of developing CAD from birth.  Complex human diseases such as CAD, diabetes, cancer etc have a polygenic genetic architecture, or they are caused by minute changes in multiple genes. These minute changes when combined with environmental and lifestyle factors can lead to disease. For decades researchers have been searching for genomic changes that might explain why only some people develop a particular disease. Genome-wide association studies have enabled researchers to identify these genetic variants associated with diseases. Most recently, they have been able to combine and score the polygenic risk by quantitating these small effect variants in the form of a Polygenic score. This score may be used to estimate an individual’s lifetime diseases such as CAD, diabetes, cancer etc.

CAD is a complex disease, onset of which is regulated by the complex interplay for multiple genetic and environmental factors. It is a condition in which the blood vessels that supply the heart with blood, oxygen, and nutrients (called coronary arteries) get blocked due to deposition of a waxy material called plaque, which prevents oxygenated blood to reach the heart and can lead to a heart attack. As of date the focus has been on the environmental and lifestyle factors to prevent the risk of CAD. Now we also know the polygenic risk that regulates this disease and with a PRS scoring model this polygenic risk can be quantified.

Existing risk prediction models incorporate information about age, sex, and clinical history (hypertension, blood cholesterol, smoking history, and history of diabetes) to calculate the probability of a CAD event. Certain models have proven to underestimate the risk of CAD in genetically predisposed Indian population. A recent study published in the Journal of American College of Cardiology has been able to validate PRS score in the Indian population. This study done by researchers from MedGenome, Harvard Medical School, Narayana Institute of Cardiac Health, Eternal Heart Institute and Madras Medical Mission has shown that PRS for CAD in the Indian population has a specificity of nearly 90%. This study has not only proved the effectiveness of the PRS concept in the Indian setting but also laid the groundwork for developing PRS for other complex diseases in India.

With the increasing focus on personalized medicine, modeling of PRS for complex diseases becomes more relevant, especially for diseases that have been long known as “lifestyle diseases”, like coronary artery disease, diabetes, etc. A PRS test using your blood/saliva sample can estimate your polygenic risk and identify measures for corrective action much earlier. When combined with other data, it might be possible to predict risk and prevent the harmful outcome, years or decades in advance.

If clinicians had access to this information, it would enable them to offer the same counseling and interventions that they do for patients meeting other high-risk criteria. Thus, reducing the burden of CAD among the young population in India.

  • The author of this article is Dr. Sanghamitra Mishra, Senior Scientist, MedGenome Labs