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 naive 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.

Automated summary

This study utilizes single-cell RNA sequencing to uncover the genetic drivers of interindividual variation in the human immune system. The researchers identify specific loci that have cell type-specific effects on gene expression and demonstrate dynamic allelic effects in B cells. Additionally, they use Mendelian randomization to determine the causal route by which risk loci contribute to autoimmune disease at the cellular level.