HCA Data Explorer

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

Updated January 30, 2023

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.

None
Seyhan Yazar1
Jose Alquicira-Hernandez1
Kristof Wing2
Anne Senabouth1
M Grace Gordon3
Stacey Andersen4
Qinyi Lu2
Antonia Rowson2
Thomas R P Taylor2
Linda Clarke5
Katia Maccora2
Christine Chen6
Anthony L Cook7
Chun Jimmie Ye3
Kirsten A Fairfax2
Alex W Hewitt2
Joseph E Powell1
1Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
2Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
3Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
4Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
5Centre for Eye Research Australia, University of Melbourne, East Melbourne, VIC, Australia.
6Department of Surgery, School of Clinical Science at Monash Health, Monash University, VIC, Australia.
7Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia.
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/f2078d5f-2e7d-4844-8552-f7c41a231e52
None
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Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

eQTLAutoimmune

Species

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

false

Analysis Protocol

analysis_protocol_1, analysis_protocol_2

File Format

4 file formats

Cell Count Estimate

1.3M

Donor Count

953
fastq.gz225 file(s)h5ad1 file(s)tar1 file(s)xlsx1 file(s)