This disorder often moves quietly through family lines for many years. Although effective treatments exist, people who are not diagnosed remain at increased risk for heart attacks and strokes.

Cardiovascular disease continues to be the top cause of death in the United States, affecting millions annually. It includes coronary artery disease, heart failure and stroke, and high cholesterol is one of its major risk factors.

According to the study, published in Circulation: Genomic and Precision Medicine, expanding routine screening could help detect most people living with this genetic condition and ultimately reduce the likelihood of severe outcomes.

Large Study Shows Most Cases Go Unnoticed

Researchers discovered that nearly 90% of participants with familial hypercholesterolemia would not have been selected for standard genetic testing. Many learned they had the condition only after DNA analysis conducted through a Mayo Clinic population-based research program. Roughly 1 in 5 had already developed coronary artery disease.

“Our findings expose a blind spot in current national guidelines, which rely on cholesterol levels and family history to determine who should receive genetic testing,” says Niloy Jewel Samadder, M.D., the study’s lead author and a Mayo Clinic gastroenterologist and cancer geneticist at the Mayo Clinic Comprehensive Cancer Center. “If we can find those at risk of cardiovascular disease early, we can treat it early and change its course and likely save lives.”

Familial hypercholesterolemia is one of the most common genetic disorders, affecting an estimated 1 in 200 to 250 people around the world. It leads to very high levels of low-density lipoprotein (LDL) cholesterol — the “bad” cholesterol — beginning at birth.

Genome Analysis Reveals Hidden Risk

The study used exome sequencing, which examines the protein-coding sections of the genome — areas where most disease-causing mutations occur. More than 84,000 people at Mayo Clinic locations in Arizona, Florida and Minnesota participated through the Tapestry DNA research study, part of the organization’s broader effort to bring genomics into routine medical care.

Out of these participants, the team identified 419 people with genetic variants known to cause familial hypercholesterolemia. Nearly 75% of them would not have met existing clinical guidelines for testing based on their cholesterol levels or reported family history, highlighting a significant gap in prevention.

Bringing Genetic Screening Into Preventive Medicine

Dr. Samadder says moving genetic screening into everyday care is the next essential step, allowing high-risk individuals to be identified earlier and treated sooner.

This effort is central to Mayo Clinic’s Precure strategic priority, which focuses on predicting and preventing serious diseases before they advance. Through technology-driven approaches and large, population-based studies, Precure aims to deliver prevention-centered care to patients as early as possible.