MedGenome Labs, India’s leading genomics and clinical data-driven diagnostics and research company, has conducted a first-ever study on Indian population that validates a novel ‘CAD-PRS’(coronary artery disease-genome-wide polygenic risk score) to precisely predict the risk of developing a coronary artery disease/myocardial infarction (MI) using a person’s genetic makeup.

MedGenome Labs collaborated with researchers from Broad Institute of MIT and Harvard; Massachusetts General Hospital, Boston;Narayana Health, Bangalore;Eternal Hospital, Jaipur; Madras Medical Mission, Chennai; KMCH, Coimbatoreand a few otherinstitutesto conduct this first-ever research capturing the PRS of disease for South Asia populations and its findings are now published in the Journal of the American College of Cardiology (JACC).

Study is based on the principle of Genome-wide Polygenic Risk Score (PRS):

This unique study is based on the principle of Genome-wide Polygenic Risk Score (PRS) which uses a genome-wideanalysis of an individual to quantify the risk of developing heart disease. It was conducted on the south Asian population in 1800 confirmed CAD cases and 1163 control samples from five centres across the country with a median age between 54 and 55 years. The findings of this study have helped develop a CAD PRS that integrates information from millions of sites of common DNA variation into a single metric that can be calculated from birth and validate a scalable polygenic score framework in India. This finding lays the scientific and operational foundation for clinical implementation not just for CAD but for other diseases.

“CAD PRS is a powerful genetic predictor that can be used to identify individual’s at increased risk for CAD. It provides a quantified risk score based on one’s genetic makeup and predicts a patient’s risk for having an acute coronary event, such as a heart attack, before symptoms appear. CAD PRS is an important new risk factor to help physicians stratify high-risk patients and better guide treatment decisions and lifestyle interventions,”said Dr.Sekar Kathiresan, CEO, Verve Therapeutics and Professor of Medicine, Harvard Medical School, Cardiology Division, Massachusetts General Hospital.

“Looking at all the available scientific evidence and our study results we are convinced that there exists a good opportunity to combine both clinical and genetic risks (polygenic risk score based) and significantly improve the primary prevention of coronary artery disease (CAD). We firmly believe that incorporating validated genetic risk scores would help in better stratification of high-risk individuals if implemented at population level,”said Dr.Vedam Ramprasad, CEO, MedGenome Labs.

Cardiac disorders  increased in urban population:

According to a research paper published in the Journal of Genetics, the estimated prevalence of CAD disease in India is about 10.5% of the population which extrapolates to a burden of about 32 million affected individuals. Over and above, the incidence of cardiac disorders has increased from 2% to 10.5% of the urban population¹ in the past few years and early age of onset is a new countrywide trend. “South Asians no matter where they stay – in India or any other country always have higher cases of CAD than Caucasians. Even if our body structure is much leaner, smaller and thus comparatively lower food consumed compared to Caucasians, we still end up with CAD. So, it can be considered that South Asians have some genetic issue that is causing high CAD cases and hence we need to identify these genetic factors so that we are able to manage the disease in our population,” said Dr Ajit Mullasari, Director Adult Cardiology, Madras Medical Mission.

Also Read: WHY YOUNG INDIANS ARE AT AN INCREASED RISK OF HEART DISEASES?

Knowing the polygenic risk is important to individuals with a family history of CAD, hypertension, diabetes, high cholesterol level, smoking habits, alcohol consumption, stressful lifestyle, as CAD results from a combination of these factors. A poor lifestyle and high polygenic risk could be a fatal combination and may result in early-onset CAD. Such findings and methods developed can be used to screen large populations and high-risk individuals at a cost less than 5000 INR. The virtual press conference and announcement was also supported by several eminent cardiologists from across the country Dr. Ramesh Seshadri, Dr.  Julius Punnen, Dr.Varun Shetty, Dr.Bagirath Raghuraman from Narayana Institute of Cardiac Science, Bangalore, Dr. Pradeep Narayan, RTIIS, Kolkata, Dr.Rajendra N.S, Narayana Hospital, Mysore and Dr.Rajeev Gupta, EHCC Jaipur.

What is Polygenic Risk Score?

Genetic research over the past decade has realized that our risk for many common conditions such as heart disease and diabetes are not influenced by just one gene, or even a handful of them. Instead, multiple genes work in tandem to influence our risk for diseases. Many small-effect genetic variations contribute to a person’s susceptibility to CAD. Polygenic Risk Score prediction quantifies the contributing effects into a score and estimates whether the tested individual is at a high and moderate risk of CAD.

 Summary of the study findings:

1. A genome-wide polygenic score (GPS) for CAD integrates information from >6 million sites of common DNA variation into a single metric-available from birth – of inherited risk

2. Study validates a scalable polygenic score framework in India which is applicable to the South Asia ethnicity, laying the scientific and operational foundation for clinical implementation at an affordable cost

 3. Results suggest feasibility for the transfer of polygenic scores across varying environmental exposures

High positive predictive value of ~90% (n= 1800, Control n= 1163)

 About Medgenome Labs:

MedGenome is a genomics and clinical data driven diagnostics and drug discovery research company founded in 2013. With the state-of-the-art Next Generation Sequencing (NGS) facility, MedGenome is one of the highest throughput NGS sequencing & CAP accredited lab in South Asia. MedGenome offers comprehensive diagnostic solutions to researchers, doctors and hospitals and its belief in continuous innovation has led to the development of many new genetic tests. MedGenome’s clinical, phenotypic and genomics data, provide insights into complex diseases and aid in drug discovery. MedGenome, a founding member of Genome Asia 100K, initiated to sequence 100,000 Genomes in the Asian Population to create gene-pool data for higher research purposes.

 References

1. Jayashree S., Arindam M. and Vijay K. V. 2015 Genetic epidemiology of coronary artery disease: an Asian Indian perspective. J. Genet. 94, 539–549

2. Mohan V, Deepa R, Rani SS, et al. Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). J Am CollCardiol 2001;38:682-7. 10.1016/S0735-1097(01)01415-2

3. Gupta, Rajeev. “Recent trends in coronary heart disease epidemiology in India.” Indian heart journal 60.2 Suppl B (2008): B4-18.

4. Enas, Enas A., and A. Senthilkumar. “Coronary Artery Disease in Asian Indians: An Update and Review.” (2001).

The post Genetic risk score for heart disease in South Asia- experts develop a new breakthrough appeared first on Health Vision.

When the heart recovers from injury, the blood flowing through its vessels is essential. But lymph – the colorless fluid that circulates in a parallel network – and the lymphatic vessels in which it moves are just as crucial, according to researchers at the Weizmann Institute of Science. They showed that without an adequate network of lymphatic vessels, the hearts of zebra fish – which can completely regenerate following injury – fail to heal, even in the presence of blood vessels. The researchers also identified two distinct types of lymphatic vessels in the fish heart, which form by different mechanisms and perform different tasks.These findings may help develop new ways for promoting heart repair and facilitating the growth of organs for transplant.

The body’s network of lymphatic vessels serves as a conduit for immune cells and drains fluid, as well as providing individual services to various organs. Prof. Karina Yaniv of Biological Regulation Department and her team wanted to learn what role the lymphatic vessels play in the heart, particularly following injury. Zebrafish are perfect for exploring this question because unlike mammals, they have a remarkable capacity for heart regeneration: Within approximately two months after being injured, up to one-third of their heart tissue can regrow without scarring. An injured mammalian heart, in contrast, does not naturally regenerate at all, instead forming scar tissue at the injury site.

In earlier research, Prof. Yaniv and colleagues had shown that in the zebra fish embryo, lymphatic vessels form by two separate mechanisms: either by sprouting and growing from pre-existing vessels, or by differentiating from progenitor cells called angioblasts. In the new study, the researchers found that in adult zebra fish, these two mechanisms are recapitulated. Moreover, each set of lymphatic vessels features its own genetic markers and responds to its own molecular signals. The scientists found that both distinct types of lymphatic vessels are also found in the hearts of mice, indicating that the disparate mechanisms by which they develop have been conserved in the course of evolution.

The researchers then asked whether either or both types play a role in regeneration. After injuring the hearts of zebra fish, Yaniv and her group discovered that the hearts’ regenerating area contained lymphatic vessels of just one type – those derived from isolated lymphatic cells, rather than vessels. These cells then merged together into vessels. Although these vessels eventually connected with the larger lymphatic vessels that belong to the other type, they remained distinct. Thus, the experiments revealed that the two types of lymphatic vessels perform different functions in the heart: It is evidently mainly the progenitor cell-derived ones that contribute to heart regeneration after injury.

Research may in the future help to grow heart tissue :

The researchers then showed that, in fact, these lymphatic cells do more than facilitate heart regeneration – the process cannot take place without them. When the scientists studied mutant zebra fish with no lymphatic vessels at all, the hearts of these mutants failed to regenerate after injury even though their blood vessels were entirely normal. “We’ve shown that the lymphatic system plays a crucial role in heart regeneration in the zebrafish,” says Prof. Yaniv. “By clarifying this role further, we may learn what the fish heart ‘knows’ about regeneration that the mammalian one doesn’t, and use this knowledge to heal human hearts.”

A more detailed understanding of this role may indeed help develop new ways of preventing scarring and promoting healing after heart attacks or other types of injury to the heart muscle. In addition, knowing exactly how the lymphatic system contributes to heart muscle growth may in the future help to grow heart tissue in laboratory conditions for the purposes of transplantation.

Study authors included Dr. Dana Gancz, Gal Perlmoter, Dr. Jonathan Semo, Hila Raviv and Noga Moshe of Biological Regulation Department; Brian C Raftrey and Prof. Kristy Red-Horse of Stanford University; Dr. Rubén Marín-Juez, Prof. Ryota L. Matsuoka and Prof. Didier Y. R. Stainier of the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Dr. Ravi Karra and Prof. Kenneth D. Poss of Duke University; and Dr. Yoseph Addadi and Ofra Golani of Weizmann’s Life Sciences Cored Facilities Department.

Prof. Karina Yaniv’s research is supported by the Maurice and Vivienne Wohl Biology Endowment; the estate of Emile Mimran; and the European Research Council. Prof. Yaniv is the incumbent of the Enid Barden and Aharon J. Jade Professorial Chair in Memory of Canter John Y. Jade. http://wis-wander.weizmann.ac.il/

The post Fish Heart findings may help develop new ways for promoting heart repair appeared first on Health Vision.