HTRA1 and Hypertension: Most (>95%) SVD is nonheritable, or sporadic, although over 50 genetic loci associated with the risk of sporadic SVD have emerged from genome-wide association studies in recent years.13–15 Heritable, monogenic forms of SVD include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; due to mutations in NOTCH3), CARASIL (HTRA1), and collagen-IV (COL4A1/COL4A2).14 Relative to the prevalent, sporadic SVD, these are rare, less strongly associated with hypertension and detected clinically in younger people, usually with more severe disease.