Burden of Dilated Perivascular Spaces, an Emerging Marker of Cerebral Small Vessel Disease, Is Highly Heritable.
Stroke
; 49(2): 282-287, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29311265
ABSTRACT
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Doenças de Pequenos Vasos Cerebrais
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Acidente Vascular Cerebral Lacunar
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Stroke
Ano de publicação:
2018
Tipo de documento:
Article