TY - JOUR
T1 - Burden of dilated perivascular spaces, an emerging marker of cerebral small vessel disease, is highly heritable
AU - Duperron, Marie Gabrielle
AU - Tzourio, Christophe
AU - Sargurupremraj, Muralidharan
AU - Mazoyer, Bernard
AU - Soumaré, Aïcha
AU - Schilling, Sabrina
AU - Amouyel, Philippe
AU - Chauhan, Ganesh
AU - Zhu, Yi Cheng
AU - Debette, Stéphanie
N1 - Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - 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 (rg=0.41±0.28; P=0.096), which seemed driven by dPVS in basal ganglia (rg=0.72±0.61; P=0.126) and not dPVS in white matter (rg=-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.
AB - 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 (rg=0.41±0.28; P=0.096), which seemed driven by dPVS in basal ganglia (rg=0.72±0.61; P=0.126) and not dPVS in white matter (rg=-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.
KW - Brain
KW - Cerebral small vessel diseases
KW - Humans
KW - Leukoaraiosis
KW - Magnetic resonance imaging
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UR - http://www.scopus.com/inward/citedby.url?scp=85044095466&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.117.019309
DO - 10.1161/STROKEAHA.117.019309
M3 - Article
C2 - 29311265
AN - SCOPUS:85044095466
SN - 0039-2499
VL - 49
SP - 282
EP - 287
JO - Stroke
JF - Stroke
IS - 2
ER -