Statistical Bioinformatics Webinar: Yazar -- Single-cell eQTL Mapping Identifies Cell-type Specific Control of Complex Disease

Genome-wide association studies in large populations have enriched our understanding of
genetic variants implicated in health and disease while expression quantitative trait
loci (eQTL) studies with microarray and bulk-RNA sequencing data showed us how these
genetic variants affect the expression of one or more genes in a tissue-specific
manner.  However, it is much less known how genetic variants influence gene expression
in various cell types within a tissue.  This study, therefore, set to identify the
cell-specific eQTLs in the human immune cells using single-cell sequencing technology.
We have performed conditional cis-eQTL analysis on 14 cell types in 1242226 immune cells
from 993 healthy human subjects and identified thousands of independent cis-eQTLs across
14 different immune cell types.  We show that the majority of these eQTL were unique to
an individual cell-type; however, eQTLs shared across the hematopoietic lineage are also
identified.  Linking GWAS variants with cis-eQTLs within different cell types, we were
able to show disease variants exert their effects in specific cell types.  We have shown
cell-specific control of immune system disease and established a healthy immune cell
resource at single-cell resolution to prioritise disease-associated variants in
functional studies.