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Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk

Published version
Peer-reviewed

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Authors

Tang, Howard H. F. 
Teo, Shu Mei 
Mok, Danny 

Abstract

Abstract: Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4+ T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis-eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2, HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.

Description

Keywords

Article, /631/208/199, /631/208/212/2019, /13/106, /38/39, /45/22, /45/61, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Nature Publishing Group UK
Sponsorship
Department of Health | National Health and Medical Research Council (NHMRC) (1049539, 1061435, 1061409)