B4081 - Identifying master regulators of gene expression in human immune cells - 16/06/2022

B number: 
Principal applicant name: 
Kaur Alasoo | University of Tartu, Institute of Computer Science (Estonia)
Krista Freimann
Title of project: 
Identifying master regulators of gene expression in human immune cells
Proposal summary: 

Common genetic variants that differ between individuals in a population lead to millions of ‘natural experiments’ that can be used to gain insight into the principles of how our immune system works. However, most published studies relying on this information have been too small take full advantage of these natural experiments. In this project, we plan to assemble genetic variation and gene expression data from up 10-15 individual studies that have all profiled multiple cell types of our immune system. We expect that joint analysis of these data will help us to identify master regulators gene expression - genes that control the activity patterns of other genes - and help us understand how these genes contribute to complex immune-mediated disorders.

Impact of research: 
Previous studies using gene expression data from whole blood (e.g. the eQTLGen Consortium) have demonstrated that although trans-eQTLs are very common, due to their small effect sizes very large sample sizes are needed to detect them. However, an important limitation of trans-eQTL analysis in whole blood is that genetically controlled cell type composition changes will give rise to many spurious trans-eQTLs that are difficult to control for computationally. These spurious associations can be overcome by using data from isolated cell type (e.g. LCLs), but most current studies have been severely underpowered. By performing trans-eQTLs analysis across ~2500 samples from the same cell type we will be able systematically map cell-type-specific trans effects on gene expression. This can reveal important master regulators controlling gene expression levels in activated human immune cells.
Date proposal received: 
Thursday, 2 June, 2022
Date proposal approved: 
Thursday, 16 June, 2022
Genetics, Infection, Cell culture, GWAS, Microarrays, RNA, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Expression, Genomics, Genome wide association study