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A computational method for Cell type-specific Expression Quantitative Trait Loci mapping using bulk RNA-seq data

Little, P.; Liu, S.; Zhabotynsky, V.; Li, Y.; Lin, D.; Sun, W.

2023-03-31 genomics
10.1101/2022.03.31.486605 bioRxiv
Show abstract

Mapping cell type-specific gene expression quantitative trait loci (ct-eQTLs) is a powerful way to investigate the genetic basis of complex traits. A popular method for ct-eQTL mapping is to assess the interaction between the genotype of a genetic locus and the abundance of a specific cell type using a linear model. However, this approach requires transforming RNA-seq count data, which distorts the relation between gene expression and cell type proportions and results in reduced power and/or inflated type I error. To address this issue, we have developed a statistical method called CSeQTL that allows for ct-eQTL mapping using bulk RNA-seq count data while taking advantage of allele-specific expression. We validated the results of CSeQTL through simulations and real data analysis, comparing CSeQTL results to those obtained from purified bulk RNA-seq data or single cell RNA-seq data. Using our ct-eQTL findings, we were able to identify cell types relevant to 21 categories of human traits.

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