On the Utility of Gene Set Methods in Genomewide Association Studies of Quantitative Traits
On the Utility of Gene Set Methods in Genomewide Association Studies of Quantitative Traits
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DOI：
10.1002/gepi.20334
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发表时间：
2008-11-01
影响因子：
2.1
通讯作者：
Chasman, Daniel I.
中科院分区：
文献类型：
--
作者：
Chasman, Daniel I.
在全基因组遗传关联研究中，先前的生物学知识可能有助于区分真正与数量性状相关的变异和绝大多数不相关的变异，这些变异可能因偶然而在假设检验中具有重要意义。然而，将现有生物学知识整合到关联研究中的正式方法最近才被提出，并且其潜在效用尚未得到彻底评估。在此，来自基因表达数据的全基因组分析的基因集方法适用于数量性状的全基因组遗传分析。所提出的基因集方法在包含多达 500 个总变体的基因集模拟中进行了测试，其中多达 20 个共同解释了 5% 的方差。在 1,000 个个体的群体中，基因集方法在检测这些基因集中真正相关的变异方面比仅依赖 P 值的相对校准的传统方法更有效。虽然极强的关联性仍然最好通过传统方法来识别，但基因集方法可以提供一种补充分析模式，以揭示影响数量性状的全部基因。热内特.流行病。 32:658-668, 2008。(C) 2008 Wiley-Liss, Inc.
In genomewide genetic association studies, prior biological knowledge may help distinguish variation that is truly associated with a quantitative trait from the vast majority of unassociated variation that may be significant in hypothesis testing due to chance. However, formal methods for integrating prior biological knowledge into association studies have only been proposed recently, and their potential utility has not been thoroughly evaluated. Herein, gene set methods from genomewide analysis of gene expression data are adapted for application to genomewide genetic analysis of quantitative traits. The proposed gene set method was tested in simulations with gene sets that included up to 500 total variants, among which up to 20 collectively explained 5% of the variance. In a population of 1,000 individuals, the gene set method was largely more efficient at detecting truly associated variants in these gene sets than a comparably calibrated conventional approach relying on P-values alone. While extremely strong associations remain best identified by conventional methods, the gene set approach may provide a complementary mode of analysis for revealing the full spectrum of genes that influence a quantitative trait. Genet. Epidemiol. 32:658-668, 2008. (C) 2008 Wiley-Liss, Inc.