A normal cholesterol report can be reassuring. So can healthy blood pressure, normal blood sugar and a fit-looking body. But these tests cannot tell the whole story. Some people carry an inherited tendency towards coronary artery disease that may remain hidden until serious disease develops. Genetic testing, particularly polygenic risk scores, is now being studied as one way to uncover that hidden layer of risk.
When the usual reports look normal
Dr Ramesh Menon, Director of Personal Genomics and Genomic Medicine, MedGenome, shared the case of a 31-year-old man from West Bengal who arrived with severe chest pain.He was not diabetic. His lipid profile was close to optimal, and routine metabolic tests did not raise concern. Yet further investigations found significant coronary artery disease, and he eventually required bypass surgery.His family history offered an important clue. His father and two paternal uncles had developed premature coronary artery disease and undergone bypass surgery at young ages.“Coronary artery disease is a polygenic disorder. Risk is shaped not by a single gene but by hundreds, sometimes thousands, of genetic variants distributed across the genome. Each variant has a modest effect, but together they have cumulative significant impact on lifetime susceptibility,” Dr Menon explained.What a DNA risk score actually measuresA polygenic risk score does not look for one “heart disease gene”. Instead, it combines the effects of many genetic variants linked with coronary artery disease.Research published through the US National Library of Medicine’s PubMed, including a meta-analysis involving nearly 980,000 participants, found that higher polygenic risk scores were associated with greater coronary artery disease risk.Importantly, this does not mean a high score guarantees a heart attack. It indicates that inherited susceptibility may be higher than average.
Why this may matter for South Asians
The question becomes particularly relevant for Indian and other South Asian populations. Researchers have developed a South Asian-specific coronary artery disease genetic score using millions of DNA variants. In studies involving South Asian participants from the UK, Bangladesh and India, people in the highest genetic-risk groups had substantially higher odds of coronary artery disease than those in the middle range.That research matters because genetic scores do not perform equally well across every ancestry. A score developed mainly from one population may not accurately represent another.
One family’s results changed the picture
The West Bengal patient’s family underwent genetic assessment. His father, who had bypass surgery at 36, also had a high polygenic risk. His mother had moderate genetic risk, while his younger sister fell within the average range.Then came the result of his 25-year-old brother.He had no symptoms and no obvious abnormalities on routine evaluation. Yet his polygenic risk score suggested an inherited coronary artery disease risk even higher than that of his older brother, who had already suffered a heart attack in his early thirties.That result did not diagnose future heart disease. Instead, it gave doctors another reason to monitor him closely and address changeable risks early.
DNA is another piece, not the whole answer
Genetic testing should not replace cholesterol checks, blood pressure monitoring, diabetes screening, family history or lifestyle assessment. The evidence supports polygenic scores as a risk-enhancing tool, not a crystal ball. Researchers are still studying how best to use these scores in everyday clinical practice.For someone with several relatives affected by premature coronary disease, however, DNA may provide information that a routine health check cannot capture.Medical experts consultedThis article includes expert inputs shared with TOI Health by:Dr Ramesh Menon, Director of Personal Genomics and Genomic Medicine, MedGenome.Inputs were used to explain how genetic factors can influence heart disease risk and why DNA-based risk assessment may provide additional insight beyond routine health checks.
