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利用等位基因表达数据检测顺式作用调控 SNP。

Detection of cis-acting regulatory SNPs using allelic expression data.

机构信息

Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

出版信息

Genet Epidemiol. 2011 Sep;35(6):515-25. doi: 10.1002/gepi.20601. Epub 2011 Jul 18.

Abstract

Allelic expression (AE) imbalance between the two alleles of a gene can be used to detect cis-acting regulatory SNPs (rSNPs) in individuals heterozygous for a transcribed SNP (tSNP). In this paper, we propose three tests for AE analysis focusing on phase-unknown data and any degree of linkage disequilibrium (LD) between the rSNP and tSNP: a test based on the minimum P-value of a one-sided F test and a two-sided t test (proposed previously for phase-unknown data), a test the combines the F and t tests, and a mixture-model-based test. We compare these three tests to the F and t tests and an existing regression-based test for phase-known data. We show that the ranking of the tests based on power depends most strongly on the magnitude of the LD between the rSNP and tSNP. For phase-unknown data, we find that under a range of scenarios, our proposed tests have higher power than the F and t tests when LD between the rSNP and tSNP is moderate (∼0.2<<∼0.8). We further demonstrate that the presence of a second ungenotyped rSNP almost never invalidates the proposed tests nor substantially changes their power rankings. For detection of cis-acting regulatory SNPs using phase-unknown AE data, we recommend the F test when the rSNP and tSNP are in or near linkage equilibrium (<0.2); the t test when the two SNPs are in strong LD (<0.7); and the mixture-model-based test for intermediate LD levels (0.2<<0.7).

摘要

等位基因表达(AE)不平衡可以用来检测个体中转录 SNP(tSNP)杂合状态下顺式作用调控 SNP(rSNP)的顺式作用调控 SNP(rSNP)。在本文中,我们提出了三种针对 AE 分析的检验方法,重点是针对相位未知数据和 rSNP 与 tSNP 之间任何程度的连锁不平衡(LD):一种基于单侧 F 检验和双侧 t 检验的最小 P 值的检验(先前针对相位未知数据提出),一种结合 F 和 t 检验的检验,以及一种基于混合模型的检验。我们将这三种检验方法与 F 和 t 检验以及现有的针对相位已知数据的基于回归的检验方法进行了比较。我们表明,基于功效的检验排序主要取决于 rSNP 与 tSNP 之间 LD 的大小。对于相位未知数据,我们发现,在一系列场景下,当 rSNP 与 tSNP 之间的 LD 适中(∼0.2<<∼0.8)时,与 F 和 t 检验相比,我们提出的检验方法具有更高的功效。我们进一步证明,第二个未分型 rSNP 的存在几乎不会使所提出的检验无效,也不会大大改变其功效排序。对于使用相位未知 AE 数据检测顺式作用调控 SNP,我们建议当 rSNP 和 tSNP 处于或接近连锁平衡(<0.2)时使用 F 检验;当两个 SNP 处于强 LD(<0.7)时使用 t 检验;对于中间 LD 水平(0.2<<0.7),使用基于混合模型的检验。

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