The University of Pittsburgh School of Medicine led a team of international scientists who developed the world’s first comprehensive genetic resource to identify people at risk of elevated ‘bad’ cholesterol — a major cause of heart disease and stroke. Published in Science, the study could help doctors predict heart attacks long before symptoms appear and guide preventive care for millions.

Heart disease remains the leading cause of death globally, claiming nearly 700,000 lives every year in the United States alone. While lifestyle factors, such as diet and exercise, play a role, researchers emphasise that genetics often dictates how the body processes cholesterol. The new resource focuses on tiny variations in the gene responsible for producing LDL receptors—the molecular gatekeepers that help clear low-density lipoprotein (LDL), commonly known as "bad" cholesterol, from the bloodstream.

“Even with normal LDL levels, a person might face elevated risk due to harmful variants in the LDL receptor,” explained Professor Frederick Roth, the study’s senior author. “By identifying these variants, clinicians can act early to prevent future heart problems.”

The research team analysed nearly 17,000 different modifications in the LDL receptor gene, measuring how each change affects the protein's ability to clear cholesterol. Their work now offers doctors an evidence-based table to interpret genetic test results, similar to how BRCA1 mutation screening transformed cancer prevention. According to co-author Dr Dan Roden, this approach could increase the detection of inherited high cholesterol disorders by up to tenfold.

Beyond Western populations, the findings carry deep relevance for South Asia — a region with one of the highest global rates of early heart attacks. Research indicates that inherited lipid disorders like familial hypercholesterolaemia contribute to one in five premature cardiac deaths in India. Yet genetic screening remains rare, often limited to urban hospitals. Public health experts believe that integrating such genomic tools could revolutionise early diagnoses in India, Pakistan, Bangladesh, and Sri Lanka.

The study forms part of the Atlas of Variant Effects Alliance, a global initiative involving more than 500 scientists from 50 countries, aimed at decoding the genetic variations that drive major diseases. Researchers hope the new LDL receptor map will soon guide more personalised, preventive heart care worldwide.