Repository logo
 

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

Accepted version
Peer-reviewed

No Thumbnail Available

Type

Article

Change log

Authors

Tang, Howard 
Teo, Shu Mei 

Abstract

Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we collected cord blood samples from a birth cohort and mapped expression quantitative trait loci (eQTLs) in resting monocytes and CD4 + T cells as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis -eQTLs were largely specific to cell type or stimulation, and response eQTLs were identified for 31% of genes with cis -eQTLs (eGenes) in monocytes and 52% of eGenes in CD4 + T cells. We identified trans -eQTLs and mapped cis regulatory factors which act as mediators of trans effects. There was extensive colocalisation of causal variants for cell type- and stimulation-specific neonatal cis -eQTLs and those of autoimmune and allergic diseases, in particular CTSH (Cathepsin H) which showed widespread colocalisation across diseases. Mendelian randomisation showed causal neonatal gene transcription effects on disease risk for BTN3A2 , HLA-C and many other genes. Our study elucidates the genetics of gene expression in neonatal conditions and cell types as well as the aetiological origins of autoimmune and allergic diseases.

Description

Keywords

31 Biological Sciences, 32 Biomedical and Clinical Sciences, 3105 Genetics, 3204 Immunology, Prevention, Genetics, Pediatric, 2 Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, 3 Good Health and Well Being

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Nature Research

Rights

All rights reserved
Sponsorship
S.C.R. are funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]