Haldar Tanushree, Ghosh Saurabh
Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata 700 108, India.
J Genet. 2015 Dec;94(4):619-28. doi: 10.1007/s12041-015-0563-4.
Clinical end-point traits are usually governed by quantitative precursors. Hence, there is active research interest in developing statistical methods for association mapping of quantitative traits. Unlike population-based tests for association, family-based tests for transmission disequilibrium are protected against population stratification. In this study, we propose a logistic regression model to test the association for quantitative traits based on a trio design. We show that the method can be viewed as a direct extension of the classical transmission diequilibrium test for binary traits to quantitative traits. We evaluate the performance of our method usingextensive simulations and compare it with an existing method, family-based association test. We found that the two methods yield comparable powers if all families are considered. However, unlike FBAT, which yields an inflated rate of false positives when noninformative trios with all three individuals' heterozygous are removed, our method maintains the correct size without compromising too much on power. We show that our method can be easily modified to incorporate multivariate phenotypes. Here, we applied this method to analyse a quantitative endophenotype associated with alcoholism.
临床终点性状通常由定量前体决定。因此,对于开发用于数量性状关联定位的统计方法有着积极的研究兴趣。与基于群体的关联检验不同,基于家系的传递不平衡检验可防止群体分层。在本研究中,我们提出了一种逻辑回归模型,用于基于三人设计检验数量性状的关联。我们表明,该方法可视为经典的二元性状传递不平衡检验对数量性状的直接扩展。我们使用大量模拟评估了我们方法的性能,并将其与现有方法——基于家系的关联检验进行了比较。我们发现,如果考虑所有家系,这两种方法具有相当的检验效能。然而,与FBAT不同,当去除所有三个个体均为杂合子的无信息三人组时,FBAT会产生过高的假阳性率,而我们的方法在不损失太多检验效能的情况下保持了正确的检验规模。我们表明,我们的方法可以很容易地修改以纳入多变量表型。在此,我们应用该方法分析了与酒精中毒相关的定量内表型。