AIMS:We introduce a family-based confidence set inference (CSI) method that can be used in preliminary genome-wide association studies to obtain confidence sets of SNPs that contribute a specific percentage to the additive genetic variance of quantitative traits. METHODS:Developed in the framework of generalized linear mixed models, the method utilizes data from outbred families of arbitrary size and structure. Through our own simulation study and analysis of the Genetics Analysis Workshop 16 simulated data, we study the properties of our method and compare its performance to that of the family association method described by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. We also analyze the Framingham Heart Study data to identify SNPs regulating high-density lipoprotein levels. RESULTS:The simulation studies demonstrated that CSI yields confidence sets with correct coverage and that it can outperform the method introduced by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. Furthermore, we identified five SNPs that potentially regulate high-density lipoprotein levels: rs9989419, rs11586238, rs1754415, rs9355648, and rs9356560. CONCLUSION:The CSI method provides confidence sets of SNPs that contribute to the genetic variance of quantitative traits and is a competitive alternative to currently used family association methods. The approach is particularly useful in genome-wide association studies as it significantly reduces the number of SNPs investigated in follow-up studies.

译文

目的:我们引入一种基于家庭的置信度集推断(CSI)方法,该方法可用于初步的全基因组关联研究,以获取对定量性状的加性遗传方差贡献特定百分比的SNP的置信度集。
方法:该方法是在广义线性混合模型的框架内开发的,利用了任意大小和结构的远交系的数据。通过我们自己的模拟研究和对Genetics Analysis Workshop 16个模拟数据的分析,我们研究了该方法的属性,并将其性能与Chen和Abecasis [Am J Hum Genet 2007; 81:913- 926]。我们还分析了Framingham心脏研究数据,以确定可调节高密度脂蛋白水平的SNP。
结果:仿真研究表明,CSI可以产生具有正确覆盖率的置信集,并且可以胜过Chen和Abecasis所介绍的方法[Am J Hum Genet 2007; 81:913-926]。此外,我们确定了五个可能调节高密度脂蛋白水平的SNP:rs9989419,rs11586238,rs1754415,rs9355648和rs9356560。
结论:CSI方法提供了SNP的置信度集,这些集有助于定量性状的遗传变异,并且是当前使用的家庭关联方法的竞争性替代方法。该方法在全基因组关联研究中特别有用,因为它大大减少了后续研究中研究的SNP数量。

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