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
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, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.).
Stroke. 2016 Apr;47(4):912-7. doi: 10.1161/STROKEAHA.115.012248. Epub 2016 Mar 10.
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.
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.
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)).
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.
颅内颈动脉钙化（ICAC）是中风最重要的危险因素之一。尽管已确定了一些ICAC的环境危险因素，但其遗传背景仍不清楚。
在2003年至2006年期间，来自基于人群的前瞻性鹿特丹研究的2034名参与者（平均年龄：69.6±6.8岁；51.7%为女性）接受了计算机断层扫描，以量化颅内颈内动脉的血管钙化情况。采集血样进行基因分型。将参与者的基因型推算到千人基因组参考面板，以生成遗传关系矩阵，用于估计ICAC体积的遗传力。对年龄和性别进行了调整。随后，进行全基因组关联分析以识别特定变异。
ICAC经年龄和性别调整后的遗传力（h(2)）为47%[标准误（SE）：19%；P=0.009]。全基因组关联分析在9号染色体p21.3上鉴定出一个变异（rs1537372；N=2034；P=4.75×10(-9)），在11号染色体p11.2上鉴定出1个变异（rs11038042，N=2034；P=3.27×10(-8)），它们与ICAC体积显著相关。rs1537372在716名中风患者的独立样本中得到重复验证（P合并=1.38×10(-10)）。
ICAC体积是一种可遗传的性状，部分由常见的基因变异解释。我们鉴定出了与ICAC相关的特定基因变异，鉴于ICAC在中风风险中的重要性，需要在更大规模的研究中进行重复验证，以进一步阐明其遗传基础。
