Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease

Science. 2022 Apr 8;376(6589):eabf3041. doi: 10.1126/science.abf3041. Epub 2022 Apr 8.


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.

MeSH terms

  • Alleles
  • Autoimmune Diseases* / genetics
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Leukocytes, Mononuclear*
  • Polymorphism, Single Nucleotide
  • Precursor Cells, B-Lymphoid
  • Quantitative Trait Loci
  • Sequence Analysis, RNA