Disruption of the vascular ECM has been hypothesised to be a key component in pathogenesis of cerebral small vessel disease, particularly in monogenic forms, and several of the genes implicated in this study (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1) have key roles in the ECM.70 Here, SH3PXD2A is linked to cerebral small vessel disease.