Burden of dilated perivascular spaces, an emerging marker of cerebral small vessel disease, is highly heritable

Background and Purpose - The genetic contribution to dilated perivascular space (dPVS) burden - an emerging MRI marker of cerebral small vessel disease - is unknown. We measured the heritability of dPVS burden and its shared heritability with other MRI markers of cerebral small vessel disease. Methods - The study sample comprised 1597 participants from the population-based Three City (3C) Dijon Study, with brain MRI and genome-wide genotyping (mean age, 72.8±4.1 years; 61% women). dPVS burden and lacunar brain infarcts were rated on a semiquantitative scale, whereas an automated algorithm generated white matter hyperintensity volume (WMHV). We estimated dPVS burden heritability and shared heritability with WMHV and lacunar brain infarcts using the genome-wide complex trait analysis tool, on unrelated participants, adjusting for age, sex, intracranial volume, and principal components of population stratification. Results - dPVS burden was significantly correlated with WMHV and lacunar brain infarcts, the strongest correlation being found between WMHV and dPVS in basal ganglia. Heritability estimates were h²=0.59±0.24 (P=0.007) for dPVS burden, h²=0.54±0.24 (P=0.010) for WMHV, and h²=0.48±0.81 (P=0.278) for lacunar brain infarcts. We found a nonsignificant trend toward shared heritability between dPVS and WMHV (r_g=0.41±0.28; P=0.096), which seemed driven by dPVS in basal ganglia (r_g=0.72±0.61; P=0.126) and not dPVS in white matter (r_g=-0.10±0.36; P=0.393). A genetic risk score for WMHV based on published loci was associated with increased dPVS burden in basal ganglia (P=0.031). Conclusions - We provide evidence for important genetic contribution to dPVS burden in older community-dwelling people, some of which may be shared with WMHV. Differential heritability patterns for dPVS in white matter and basal ganglia suggest at least partly distinct underlying biological processes.