A genomewide scan for early-onset coronary artery disease in 438 families: The GENECARD Study
A genomewide scan for early-onset coronary artery disease in 438 families: The GENECARD Study
复制标题
DOI：
10.1086/423900
复制
发表时间：
2004-09-01
影响因子：
9.8
通讯作者：
Kraus, WE
中科院分区：
文献类型：
--
作者：
Hauser, ER;Crossman, DC;Kraus, WE
冠状动脉疾病（CAD）的家族史，特别是当疾病发生在年轻时，是CAD的一个潜在危险因素。在两个或两个以上的兄弟姐妹在早期受到影响的家庭中收集DNA，可以通过连锁分析确定CAD的遗传因素。我们对来自438个家庭的1168个人进行了全基因组扫描，其中包括493对患病的兄弟姐妹，男性在51岁前发病，女性在56岁前发病。我们前瞻性地定义了三个家族表型亚群：(1)两个或两个以上兄弟姐妹出现急性冠状动脉综合征；(2)所有患病兄弟姐妹均无2型糖尿病；(3)任何一个兄弟姐妹有动脉粥样硬化性血脂异常。对395个微卫星标记进行基因型分析。如果区域提供参数化两点LOD评分>1.5，以及非参数多点LOD评分>1.0，则该区域被定义为提供关联证据。3q13染色体上的区域(多点LOD=3.3；经验P值
A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD=3.3; empirical P value