Genomewide linkage and peakwide association analyses of carotid plaque in Caribbean Hispanics.
Genomewide linkage and peakwide association analyses of carotid plaque in Caribbean Hispanics.
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DOI：
10.1161/strokeaha.110.596981
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发表时间：
2010-12
期刊：
影响因子：
8.3
通讯作者：
Sacco RL
中科院分区：
文献类型：
--
作者：
Dong C;Beecham A;Slifer S;Wang L;Blanton SH;Wright CB;Rundek T;Sacco RL
动脉粥样硬化是一种复杂的亚临床心血管疾病，具有相当大的遗传成分。本研究试图在2个独立样本中确定影响颈动脉斑块的遗传位点。B型超声检查颈动脉斑块的存在和面积。采用方差分量分析法对来自100个多米尼加家庭的1308名受试者的383个常染色体微卫星标记进行连锁检验。多元线性和逻辑回归模型被用来调查斑块性状和18 904个单核苷酸多态性之间的关联下的1对数的优势单位下降区域的连锁峰在一个独立的社区为基础的数据集（N=941，41%多米尼加人）从北方曼哈顿研究。校正年龄、高血压、糖尿病、香烟包年数、体重指数和腰臀比后，斑块存在（h=0.50±0.14，P<0.0001）和斑块面积（h=0.17±0.04，P<0.0001）具有显著的遗传度。数量性状连锁分析和二分性状连锁分析得到了相似的结果，并在7q36、11p15、14q32和15q23上确定了4个多点比值分数对数≥2.00的区域。在4个连锁峰的关联分析中，SOX 6、FSD 2、AP 3S2、EFTUD 1和MYOD 1中或附近的几个单核苷酸多态性与颈动脉斑块性状相关，在北方曼哈顿研究数据集中标称P≤0.0005，在北方曼哈顿研究多米尼加亚组中P≤0.01。颈动脉斑块具有相当大的遗传力，可能受染色体11p15、14q32和15q23上的位点的影响。骨形态发生蛋白通路中的SOX 6基因可能是颈动脉斑块的候选者。需要更大规模的独立研究来验证这些发现。
Atherosclerosis is a complex subclinical cardiovascular disorder with a substantial genetic component. This study sought to identify genetic loci influencing carotid plaque in 2 independent samples. B-mode ultrasound was performed to determine the presence and area of carotid plaque. Variance components analysis was used to test for linkage using 383 autosomal microsatellite markers in 1308 subjects from 100 Dominican families. Multiple linear and logistic regression models were used to investigate the association between plaque traits and 18 904 single nucleotide polymorphisms under the 1-logarithm of odds unit down regions of linkage peaks in an independent community-based data set (N=941, 41% Dominicans) from the Northern Manhattan Study. After adjustment for age, hypertension, diabetes mellitus, cigarette pack-years, body mass index, and waist-to-hip ratio, significant heritability was detected for plaque presence (h=0.50±0.14, P<0.0001) and plaque area (h=0.17±0.04, P<0.0001). Quantitative and dichotomous trait linkage analyses obtained similar results and identified 4 regions with multipoint logarithm of odds scores ≥2.00 on 7q36, 11p15, 14q32, and 15q23. In the association analysis of the 4 linkage peaks, several single nucleotide polymorphisms in or near SOX6, FSD2, AP3S2, EFTUD1, and MYOD1 were associated with carotid plaque traits with a nominal P≤0.0005 in the Northern Manhattan Study data set and with a P≤0.01 in Northern Manhattan Study Dominican subset. Carotid plaque has considerable heritability and may be influenced by loci on chromosomes 11p15, 14q32, and 15q23. The SOX6 gene within the bone morphogenic protein pathway could be a candidate for carotid plaque. Larger independent studies are needed to validate these findings.