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Quantifying the regulatory effect size of cis-acting genetic variation using allelic fold change
Genome Research ( IF 7 ) Pub Date : 2017-11-01 , DOI: 10.1101/gr.216747.116
Pejman Mohammadi , Stephane E. Castel , Andrew A. Brown , Tuuli Lappalainen

Mapping cis-acting expression quantitative trait loci (cis-eQTL) has become a popular approach for characterizing proximal genetic regulatory variants. In this paper, we describe and characterize log allelic fold change (aFC), the magnitude of expression change associated with a given genetic variant, as a biologically interpretable unit for quantifying the effect size of cis-eQTLs and a mathematically convenient approach for systematic modeling of cis-regulation. This measure is mathematically independent from expression level and allele frequency, additive, applicable to multiallelic variants, and generalizable to multiple independent variants. We provide efficient tools and guidelines for estimating aFC from both eQTL and allelic expression data sets and apply it to Genotype Tissue Expression (GTEx) data. We show that aFC estimates independently derived from eQTL and allelic expression data are highly consistent, and identify technical and biological correlates of eQTL effect size. We generalize aFC to analyze genes with two eQTLs in GTEx and show that in nearly all cases the two eQTLs act independently in regulating gene expression. In summary, aFC is a solid measure of cis-regulatory effect size that allows quantitative interpretation of cellular regulatory events from population data, and it is a valuable approach for investigating novel aspects of eQTL data sets.



中文翻译:

使用等位基因倍数变化量化顺式作用基因变异的调控效应大小

映射顺式作用表达定量性状基因座(cis -eQTL)已成为表征近端遗传调控变异的流行方法。在本文中,我们描述并描述了对数等位基因倍数变化(aFC),与给定遗传变异相关的表达变化的幅度,作为可量化顺式-eQTL效应大小的生物学解释单位和数学上方便的系统建模方法中-规定。该测量在数学上与表达水平和等位基因频率,加性无关,适用于多等位基因变体,并且可推广至多个独立变体。我们提供了从eQTL和等位基因表达数据集估算aFC的有效工具和指南,并将其应用于基因型组织表达(GTEx)数据。我们显示独立于eQTL和等位基因表达数据的aFC估计值高度一致,并确定eQTL效应大小的技术和生物学相关性。我们概括了aFC来分析GTEx中具有两个eQTL的基因,并表明几乎在所有情况下,两个eQTL在调节基因表达中均独立发挥作用。综上所述,aFC是衡量顺式的可靠方法-调节作用大小,可以从人口数据中定量解释细胞调节事件,这是研究eQTL数据集新颖方面的一种有价值的方法。

更新日期:2017-11-01
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