Genetic susceptibility to thrombosis and its relationship to physiological risk factors: The GAIT study
Genetic susceptibility to thrombosis and its relationship to physiological risk factors: The GAIT study
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DOI：
10.1086/316903
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发表时间：
2000-12-01
影响因子：
9.8
通讯作者：
Blangero, J
中科院分区：
文献类型：
--
作者：
Souto, JC;Almasy, L;Blangero, J
尽管有许多明确的遗传缺陷导致血栓形成风险增加，但关于遗传因素在一般人群血栓形成风险中的相对重要性的信息很少。我们对西班牙人群中的血栓形成遗传学进行了一项基于家庭的研究，以评估血栓形成的遗传性，并确定基因对血栓形成风险和相关定量止血表型的联合作用。我们检查了 21 个扩展谱系中的 338 个人。 12个家系通过患有特发性血栓的先证者确定，其余家系随机确定。通过使用多变量阈值模型的新型方差分量方法来估计血栓形成倾向的遗传性以及血栓形成与每个定量危险因素之间的遗传相关性。超过 60% 的常见血栓易感性变异可归因于遗传因素。一些定量风险因素与血栓形成具有显着的遗传相关性，表明影响这些生理相关性的定量变化的一些基因也会影响血栓形成的风险。与血栓形成具有显着遗传相关性的特征包括多种凝血因子（因子 VII、VIII、IX、XI、XII 和冯维勒布兰德）、组织纤溶酶原激活剂、同型半胱氨酸和活化蛋白 C 比率的水平。这是第一项量化常见血栓形成易感性遗传因素的研究。血栓形成风险的高遗传性以及血栓形成与相关危险因素之间的显着遗传相关性表明，相关定量表型的开发将有助于寻找易感基因。
Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 338 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors (factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.