A METHOD TO CORRECT FOR POPULATION STRUCTURE USING A SEGREGATION MODEL

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 为了克服基于人群的关联研究中由人群分层引起的“虚假”关联，我们提出了一种基于主成分的方法，可以同时利用家庭和不相关的样本。 更具体地说，我们采用了多变量逻辑模型，该模型通常用于分离分析，并且可以考虑家庭相关结构，以进行关联分析。 为了纠正隐藏群体结构的影响，根据标记基因型数据矩阵计算出的前十个主成分被纳入模型中作为协变量。 为了测试关联性，感兴趣的标记也作为协变量纳入模型中。 我们将所提出的方法应用于 GAW16 Framingham 心脏研究 50k 数据集中的第二代，即后代队列，以评估该方法的性能。 尽管在最大化似然函数时可能存在收敛困难（如平坦似然所示），但检验统计量的经验 P 值的分布确实表明，只要可以计算估计值的方差-协方差矩阵，该方法就具有正确的 I 类错误率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To overcome the "spurious" association caused by population stratification in population-based association studies, we propose a principal component based method that can utilize both family and unrelated samples at the same time. More specifically, we adapt a multivariate logistic model, which is often used in segregation analysis and can allow for the family correlation structure, for association analysis. To correct the effect of hidden population structure, the first ten principal components calculated from the matrix of marker genotype data are incorporated as covariates in the model. To test for the association, the marker of interest is also incorporated as a covariate in the model. We applied the proposed method to the second generation, i.e. the Offspring Cohort, in the GAW16 Framingham Heart Study 50k Data Set to evaluate the performance of the method. Although there may have been difficulty in the convergence while maximizing the likelihood function, as indicated by a flat likelihood, the distribution of the empirical P-values for the test statistic does show that the method has a correct Type I error rate whenever the variance-covariance matrix of the estimates can be computed.