Background
Familial hypercholesterolemia (FH) is a common inherited condition that causes lifelong high levels of low-density lipoprotein cholesterol (LDL-C), often called “bad cholesterol.” Because LDL-C remains elevated from birth, people with FH face a much higher risk of early atherosclerosis, heart attack, and other cardiovascular complications if the condition is not recognized and treated early. Standard care usually includes intensive lifestyle counseling, statin therapy, and, when needed, additional lipid-lowering medicines such as ezetimibe or PCSK9 inhibitors.
Most FH research has historically focused on people of European ancestry. As a result, the way we define and classify genetic variants linked to FH has been shaped heavily by European reference data. This can create problems when those same classification systems are applied to people from other ancestry groups, especially African ancestry individuals, whose genetic variation may be underrepresented in current databases. One concern is that variants of uncertain significance, or VUSs, may be more common in African ancestry groups and may not be properly recognized as clinically important.
