Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes
Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes
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DOI：
10.1086/367923
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发表时间：
2003-03-01
影响因子：
9.8
通讯作者：
Flanders, WD
中科院分区：
文献类型：
--
作者：
Yang, QH;Khoury, MJ;Flanders, WD
研究认为，基因检测将提供有限的信息来预测常见疾病的概率，因为基因型的不完全分布和一般人群的相关风险低。然而，这些研究通常一次只检查一个基因的影响。我们认为，疾病预测常见的多因素疾病，大大提高了同时考虑多个诱发遗传和环境因素，只要该模型正确地反映了潜在的疾病病因。我们展示了如何使用似然比来联合收割机结合几种基因检测的信息来计算发展为多因素疾病的概率。为了说明同时使用多种基因检测如何提高对多因素疾病的预测，我们使用模拟病例对照数据，通过logistic回归计算受多种遗传和环境风险因素影响的假设疾病的似然比。作为一个实际的例子，我们也将这种方法应用于静脉血栓形成，这是一种受多种遗传和非遗传风险因素影响的多因素疾病。在合理的条件下，同时使用多种基因检测可以显著提高疾病的预测能力。例如，同时使用一组三种基因检测（凝血因子V Leiden，凝血酶原变体G20210A和蛋白C缺乏）将静脉血栓形成检测的阳性预测值增加至少八倍。多重基因检测有可能提高常见多因素疾病预测检测的临床有效性。
Studies have argued that genetic testing will provide limited information for predicting the probability of common diseases, because of the incomplete penetrance of genotypes and the low magnitude of associated risks for the general population. Such studies, however, have usually examined the effect of one gene at time. We argue that disease prediction for common multifactorial diseases is greatly improved by considering multiple predisposing genetic and environmental factors concurrently, provided that the model correctly reflects the underlying disease etiology. We show how likelihood ratios can be used to combine information from several genetic tests to compute the probability of developing a multifactorial disease. To show how concurrent use of multiple genetic tests improves the prediction of a multifactorial disease, we compute likelihood ratios by logistic regression with simulated case-control data for a hypothetical disease influenced by multiple genetic and environmental risk factors. As a practical example, we also apply this approach to venous thrombosis, a multifactorial disease influenced by multiple genetic and nongenetic risk factors. Under reasonable conditions, the concurrent use of multiple genetic tests markedly improves prediction of disease. For example, the concurrent use of a panel of three genetic tests (factor V Leiden, prothrombin variant G20210A, and protein C deficiency) increases the positive predictive value of testing for venous thrombosis at least eightfold. Multiplex genetic testing has the potential to improve the clinical validity of predictive testing for common multifactorial diseases.