Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease
The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.
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Analysis Portals
Project Label
eQTLAutoimmuneSpecies
Homo sapiens
Sample Type
specimens
Anatomical Entity
blood
Organ Part
Unspecified
Selected Cell Types
peripheral blood mononuclear cell
Disease Status (Specimen)
normal
Disease Status (Donor)
normal
Development Stage
human adult stage
Library Construction Method
10x 3' v2
Nucleic Acid Source
single cell
Paired End
falseAnalysis Protocol
analysis_protocol_1, analysis_protocol_2File Format
Cell Count Estimate
1.3MDonor Count
1.0k