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


Yazar, S and Alquicira-Hernandez, J and Wing, K and Senabouth, A and Gordon, MG and Anderson, S and Lu, QY and Rowson, A and Taylor, TRP and Clarke, L and Maccora, K and Chen, C and Cook, AL and Ye, CJ and Fairfax, KA and Hewitt, AW and Powell, JE, Single cell eQTL mapping identifies cell type specific genetic control of autoimmune disease, Science, 376, (154) pp. 1-14. ISSN 0036-8075 (2022) [Refereed Article]

Copyright Statement

Copyright 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

DOI: doi:10.1126/science.abf3041


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.

Item Details

Item Type:Refereed Article
Keywords:scRNA-seq; expression quantitative trait loci (eQTLs)
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetic immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Wing, K (Mr Kristof Wing)
UTAS Author:Lu, QY (Mr Qinyi Lu)
UTAS Author:Cook, AL (Associate Professor Tony Cook)
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:152714
Year Published:2022
Web of Science® Times Cited:11
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2022-08-23
Last Modified:2022-09-13

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