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Single cell eQTL mapping identifies cell type specific genetic control of autoimmune disease
journal contribution
posted on 2023-05-21, 12:39 authored by Yazar, S, Alquicira-Hernandez, J, Kristof WingKristof Wing, Senabouth, A, Gordon, MG, Anderson, S, Lu, QY, Rowson, A, Taylor, TRP, Clarke, L, Maccora, K, Chen, C, Anthony CookAnthony Cook, Ye, CJ, Kirsten FairfaxKirsten Fairfax, Alexander HewittAlexander Hewitt, Powell, JEThe 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.
History
Publication title
ScienceVolume
376Issue
154Pagination
1-14ISSN
0036-8075Department/School
Menzies Institute for Medical ResearchPublisher
American Association for the Advancement of SciencePlace of publication
New YorkRights statement
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government WorksRepository Status
- Restricted