A powerful approach to test an optimally weighted combination of rare variants in admixed populations.
A powerful approach to test an optimally weighted combination of rare variants in admixed populations.
复制标题
一种强大的方法，用于测试混合群体中稀有变异的最佳加权组合。
DOI：
10.1002/gepi.21894
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发表时间：
2015
影响因子：
2.1
通讯作者：
Sha,Qiuying
中科院分区：
文献类型：
--
作者：
Wang,Xuexia;Zhang,Shuanglin;Li,Yun;Li,Mingyao;Sha,Qiuying
长期以来，群体分层一直被认为是遗传关联研究中的一个问题，因为未被认识到的群体分层可能导致假阳性和假阴性的结果，如果不适当纠正，可能会模糊真实的关联信号。在罕见变异关联分析中，这个问题可能更严重，因为罕见变异通常比常见变异表现出更强的潜在不同的分层模式。为了纠正遗传关联研究中的群体分层，我们提出了一种新的方法来测试混合群体（TOWA）中最优加权变异组合的影响，其中分析得出的最优权重可以从现有的表型和基因型数据中计算出来。TOWA增加了罕见变异和那些与表型有强烈关联的变异的权重。此外，它可以根据关联的方向进行调整，并允许研究对象之间的本地血统差异。大量的仿真结果表明，在存在人口分层的情况下，TOWA的I型错误率是可控的，并且比现有的方法更有效。我们还将TOWA应用于一个真实的测序数据。我们的模拟研究和实际数据分析结果表明，TOWA是混合群体中罕见变异关联分析的有用工具。
Population stratification has long been recognized as an issue in genetic association studies because unrecognized population stratification can lead to both false‐positive and false‐negative findings and can obscure true association signals if not appropriately corrected. This issue can be even worse in rare variant association analyses because rare variants often demonstrate stronger and potentially different patterns of stratification than common variants. To correct for population stratification in genetic association studies, we proposed a novel method to Test the effect of an Optimally Weighted combination of variants in Admixed populations (TOWA) in which the analytically derived optimal weights can be calculated from existing phenotype and genotype data. TOWA up weights rare variants and those variants that have strong associations with the phenotype. Additionally, it can adjust for the direction of the association, and allows for local ancestry difference among study subjects. Extensive simulations show that the type I error rate of TOWA is under control in the presence of population stratification and it is more powerful than existing methods. We have also applied TOWA to a real sequencing data. Our simulation studies as well as real data analysis results indicate that TOWA is a useful tool for rare variant association analyses in admixed populations.