Genessense

South Asians can now know if they are at risk for coronary artery disease – a significant milestone in Genomic medicine

Coronary Artery Disease (CAD) is one of the leading causes of death worldwide. South Asian ancestry, that accounts for 23% of global population, has been found to have increased risk for CAD compared with most other ethnicities. In view of this, practice guidelines in the United States even recognize South Asian ancestry as one of the risk-enhancing factors for CAD. Manifestation of CAD has been recognized to be multifactorial in nature, brought about by both genetic and environmental factors.

Diseases caused by mutation in a single gene are classified as monogenic in nature. The risk of CAD is said to be driven by monogenic variations that are associated with hypercholesterolemia. However, studies have shown that a vast majority of individuals with CAD do not harbor any monogenic mutations, pointing to the involvement of variations in several genes across the human genome. Hence, a polygenic approach was thought to be more relevant to estimate the risk for CAD in a population.

Recently, an algorithm was developed to estimate what is known as a Genome-wide Polygenic Score (GPS) for common diseases. Integrating 6 million sites from the human genome, it has the potential to identify individuals with risk that is comparable to monogenic mutations.

Study on South Asians

Using a GPS approach, MedGenome Labs Ltd. did a multicentric study(*) with a cohort of South Asian ancestry. A static ancestry and GPSCAD reference distribution was built using about 6.6 million common DNA variations from a study done by MedGenome Labs Ltd in collaboration with the National Institute of Biomedical Genomics (NIBMG) on 1522 individuals. PRS scores of confirmed cases of CAD and controls were compared in 3 different South Asian populations namely South Asian UK Biobank, Bangladesh and India. The study revealed significant increase in the risk for CAD in all three study cohorts.

Key results of the study

While the risk for CAD in top 5% of the GPSCAD distribution in south Asian UK Biobank participants was estimated to be 4.1 times more than that of the controls, Bangladeshi and Indian cohort were estimated to have 2.4 and 3.2 times more risk for CAD respectively. This study, titled “Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians” published in the prestigious Journal of the American College of Cardiology, is a significant step towards application of genomics in medicine and recognition of inherited risk as a relevant public health parameter.

What does the study mean to South Asians?

Risk for developing CAD is not often captured using clinical risk estimators.

Manifestation of common diseases like CAD is orchestrated by both genetic and environmental factors.

The increased genome interpretation for CAD provides greater opportunity to deliver on genomic medicine.

Polygenic scores distill inherited risk from your DNA into a single number identifying high-risk individuals.

GPS-driven risk estimation along with information on monogenic variations is more informative than monogenic mutations alone.

Study on CAD in South Asian populations reveals that polygenic scores can help identifying individuals with profound risk for CAD at an early stage and facilitate appropriate lifestyle changes and interventional treatment.

A substantial number of individuals in the working age can be saved from events like CAD-related deaths through presymptomatic risk determination. The risk prediction can be done very early in life and only once.

Preventive genomics is an insightful approach that can help to identify the need for interventions in multiple categories of the population - asymptomatic individuals with underlying pathogenic gene variants, those with symptoms or family history with appropriate interventional strategies, as well as the curious and the concerned.

Our collaborators for the study

Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
Eternal Heart Care Centre, Jaipur, India
Narayana Health, Bengaluru, India
Amrita Institute of Medical Sciences, Kochi, India
Kovai Medical Center and Hospital Research Foundation, Coimbatore, India
Madras Medical Mission, Chennai, India
MedGenome Inc., Foster City, California
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom
British Heart Foundation Centre for Research Excellence, University of Cambridge, Cambridge, United Kingdom
National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, United Kingdom
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom
Department of Human Genetics, Wellcome Sanger Institute, Hinxton, United Kingdom
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
Cambridge Baker Systems Genomics Initiative, Melbourne, Victoria, Australia, and Cambridge, United Kingdom