The Power of Single-Cell RNA Sequencing in eQTL Discovery

Genome-wide association studies have successfully mapped thousands of loci associated with complex traits. During the last decade, functional genomics approaches combining genotype information with bulk RNA-sequencing data have identified genes regulated by GWAS loci through expression quantitative trait locus (eQTL) analysis. Single-cell RNA-Sequencing (scRNA-Seq) technologies have created new exciting opportunities for spatiotemporal assessment of changes in gene expression at the single-cell level in complex and inherited conditions. A growing number of studies have demonstrated the power of scRNA-Seq in eQTL mapping across different cell types, developmental stages and stimuli that could be obscured when using bulk RNA-Seq methods. In this review, we outline the methodological principles, advantages, limitations and the future experimental and analytical considerations of single-cell eQTL studies. We look forward to the explosion of single-cell eQTL studies applied to large-scale population genetics to take us one step closer to understanding the molecular mechanisms of disease.

Automated summary

Genome-wide association studies have identified numerous loci associated with complex traits, and functional genomics approaches have further explored the genes regulated by these loci using bulk RNA-sequencing data. Single-cell RNA-Sequencing (scRNA-Seq) technologies have provided new opportunities for assessing gene expression changes at the single-cell level. In this review, the authors outline the methodological principles, advantages, limitations, and future considerations of single-cell eQTL studies.