Heritability and Genome-Wide Association Analyses of Intracranial Carotid Artery Calcification: The Rotterdam Study.
Stroke
; 47(4): 912-7, 2016 Apr.
Article
en En
| MEDLINE
| ID: mdl-26965845
ABSTRACT
BACKGROUND AND PURPOSE:
Intracranial carotid artery calcification (ICAC) is one of the most important risk factors for stroke. Although several environmental risk factors for ICAC have been identified, its genetic background remains unclear.METHODS:
Between 2003 and 2006, 2034 participants from the prospective population-based Rotterdam study (mean age 69.6±6.8 years; 51.7% female) underwent computed tomography to quantify vascular calcification in the intracranial internal carotid artery. Blood samples were drawn for genotyping. Genotypes of the participants were imputed to the 1000 Genomes reference panel to generate genetic relationship matrices for the estimation of the heritability of ICAC volume. Adjustments were made for age and sex. Subsequently, genome-wide association analyses were performed to identify specific variants.RESULTS:
The age- and sex-adjusted heritability (h(2)) of ICAC was 47% [standard error (SE) 19%; P=0.009]. Genome-wide association analyses identified a variant on chromosome 9p21.3 (rs1537372; N=2034; P=4.75×10(-9)) and 1 variant on chromosome 11p11.2 (rs11038042, N=2034; P=3.27×10(-8)) that were significantly associated with ICAC volume. Rs1537372 replicated in an independent sample of 716 stroke patients (Pcombined=1.38×10(-10)).CONCLUSIONS:
ICAC volume is a heritable trait, which is partly explained by common genetic variation. We identified specific genetic variants associated with ICAC, which given the importance of ICAC in stroke risk, needs replication in larger-scale studies to further elucidate its genetic basis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de las Arterias Carótidas
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Arteria Carótida Interna
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Predisposición Genética a la Enfermedad
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Accidente Cerebrovascular
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Calcificación Vascular
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Stroke
Año:
2016
Tipo del documento:
Article