A LARGE USA study has revealed that hundreds of people unknowingly carry genetic variants that cause familial hypercholesterolemia, a condition that greatly increases the risk of early heart disease but is highly treatable when detected. The findings show that routine genetic screening could dramatically improve diagnosis and prevention.
Genetic Screening Reveals Hidden Risk
Familial hypercholesterolemia is an inherited condition that raises levels of harmful cholesterol from birth. Although effective treatments exist, the disorder is often missed until heart disease appears. The new study, drawing on 84,413 volunteers from Minnesota, Arizona, and Florida, used exome sequencing to search for disease-causing variants in three key genes linked to the condition.
Researchers identified 419 people with a definite genetic diagnosis, about 1 in 200 participants. Most had changes in the LDLR or APOB genes, which disrupt how the body clears cholesterol from the blood. Nearly 90% had never been diagnosed before, despite carrying variants that significantly increase the risk of a heart attack at a young age.
Familial Hypercholesterolemia Diagnosed Through Genetics
Using current clinical criteria alone would have missed the majority of cases. Only 30.8% of those with a confirmed genetic diagnosis met the traditional Dutch Lipid Clinic Network score used by clinicians. This gap suggests that clinical assessments frequently fail to detect the disorder, especially in people who do not yet show obvious symptoms.
The study also found that many carriers were not receiving optimal care. More than one in four was not taking cholesterol-lowering medication, and only 10% had reached recommended cholesterol goals. A history of coronary artery disease was reported in 22.4% of carriers, highlighting the real-world consequences of missed diagnoses.
A Case for Wider Genetic Screening
By capturing subtle genetic changes invisible to routine blood tests, sequencing offers a powerful tool to identify at-risk individuals early, often decades before heart problems develop. Researchers say these findings support broader use of genetic screening, which could allow doctors to intervene sooner and prevent premature heart disease on a large scale.
Reference
Samadder NJ et al. Exome Sequencing Enhances Screening for Familial Hypercholesterolemia Within a Multi-Site Healthcare System. Circ Genom Precis Med. 2025 Nov 12:e005174. doi: 10.1161/CIRCGEN.125.005174. Epub ahead of print. PMID: 41221644.
