Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Circulation. 2009 Dec 15;120(24):2448-54. doi: 10.1161/CIRCULATIONAHA.109.865501.
Many different genetic and clinical factors have been identified as causes or contributors to atherosclerosis. We present a model of preclinical atherosclerosis based on genetic and clinical data that predicts the presence of coronary artery calcification in healthy Americans of European descent 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA).
We assessed 712 individuals for the presence or absence of coronary artery calcification and assessed their genotypes for 2882 single-nucleotide polymorphisms. With the use of these single-nucleotide polymorphisms and relevant clinical data, a Bayesian network that predicts the presence of coronary calcification was constructed. The model contained 13 single-nucleotide polymorphisms (from genes AGTR1, ALOX15, INSR, PRKAB1, IL1R2, ESR2, KCNK1, FBLN5, PPARA, VEGFA, PON1, TDRD6, PLA2G7, and 1 ancestry informative marker) and 5 clinical variables (sex, age, weight, smoking, and diabetes mellitus) and achieved 85% predictive accuracy, as measured by area under the receiver operating characteristic curve. This is a significant (P<0.001) improvement on models that use just the single-nucleotide polymorphism data or just the clinical variables.
We present an investigation of joint genetic and clinical factors associated with atherosclerosis that shows predictive results for both cases, as well as enhanced performance for their combination.
许多不同的遗传和临床因素已被确定为动脉粥样硬化的原因或促成因素。我们提出了一个基于遗传和临床数据的临床前动脉粥样硬化模型，该模型可预测欧洲裔 45 至 84 岁健康美国人中冠状动脉钙化的存在，该模型基于多民族动脉粥样硬化研究（MESA）。
我们评估了 712 个人是否存在冠状动脉钙化，并评估了他们的 2882 个单核苷酸多态性的基因型。使用这些单核苷酸多态性和相关的临床数据，构建了一个预测冠状动脉钙化存在的贝叶斯网络。该模型包含 13 个单核苷酸多态性（来自 AGTR1、ALOX15、INSR、PRKAB1、IL1R2、ESR2、KCNK1、FBLN5、PPARA、VEGFA、PON1、TDRD6、PLA2G7 基因和 1 个种族信息标记）和 5 个临床变量（性别、年龄、体重、吸烟和糖尿病），其预测准确率为 85%，通过接受者操作特征曲线下面积来衡量。这显著优于仅使用单核苷酸多态性数据或仅使用临床变量的模型（P<0.001）。
我们对与动脉粥样硬化相关的联合遗传和临床因素进行了研究，结果表明，该模型对病例具有预测作用，并且对其组合具有增强的性能。
