Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs

Nat Genet. 2018 Apr;50(4):493-497. doi: 10.1038/s41588-018-0089-9. Epub 2018 Apr 2.


Genome-wide association studies have identified thousands of genetic variants that are associated with disease 1 . Most of these variants have small effect sizes, but their downstream expression effects, so-called expression quantitative trait loci (eQTLs), are often large 2 and celltype-specific3-5. To identify these celltype-specific eQTLs using an unbiased approach, we used single-cell RNA sequencing to generate expression profiles of ~25,000 peripheral blood mononuclear cells from 45 donors. We identified previously reported cis-eQTLs, but also identified new celltype-specific cis-eQTLs. Finally, we generated personalized co-expression networks and identified genetic variants that significantly alter co-expression relationships (which we termed 'co-expression QTLs'). Single-cell eQTL analysis thus allows for the identification of genetic variants that impact regulatory networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epistasis, Genetic
  • Gene Regulatory Networks
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Leukocytes, Mononuclear / classification
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Quantitative Trait Loci*
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Transcriptome