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Heritability and Genome-Wide Association Analyses of Intracranial Carotid Artery Calcification: The Rotterdam Study.
Adams, Hieab H H; Ikram, M Arfan; Vernooij, Meike W; van Dijk, Anouk C; Hofman, Albert; Uitterlinden, André G; van Duijn, Cornelia M; Koudstaal, Peter J; Franco, Oscar H; van der Lugt, Aad; Bos, Daniel.
Afiliación
  • Adams HH; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Ikram MA; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Vernooij MW; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • van Dijk AC; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Hofman A; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Uitterlinden AG; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • van Duijn CM; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Koudstaal PJ; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Franco OH; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • van der Lugt A; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
  • Bos D; From the Departments of Epidemiology (H.H.H.A., M.A.I., M.W.V., A.H., A.G.U., C.M.v.D., O.H.F., D.B.), Radiology (M.A.I., M.W.V., A.C.v.D., A.v.d.L., D.B.), Neurology (M.A.I., A.C.v.D., P.J.K.), and Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, the Netherlands; and Department of Epidemiology, H
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades de las Arterias Carótidas / Arteria Carótida Interna / Predisposición Genética a la Enfermedad / Accidente Cerebrovascular / Calcificación Vascular Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Año: 2016 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades de las Arterias Carótidas / Arteria Carótida Interna / Predisposición Genética a la Enfermedad / Accidente Cerebrovascular / Calcificación Vascular Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Año: 2016 Tipo del documento: Article