Prevalence and clinical consequences of genetic variants associated with familial hypercholesterolemia and LDL-C lowering in a diverse patient population

Familial Hypercholesterolemia (FH) is a public health priority for diagnosis and treatment, with an estimated global prevalence of 1:300. FH is caused by loss-of-function (LOF) variants in LDLR, protein-disrupting variants in APOB, and gain-of-function variants in PCSK9. Pathogenic variants in these genes increase the risk of atherosclerosis, and untreated FH increases the risk of coronary artery disease (CAD) by up to 20-fold. Early and aggressive management with statins and other lipid-lowering therapies can mitigate associated morbidity.