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


Type
Article
Change log
Authors
Tang, Howard HF 
Teo, Shu Mei 
Mok, Danny 
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
Autoimmune Diseases, Butyrophilins, CD4-Positive T-Lymphocytes, Cathepsin H, Child, Child Development, Child, Preschool, Datasets as Topic, Fetal Blood, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-C Antigens, Humans, Hypersensitivity, Infant, Infant, Newborn, Mendelian Randomization Analysis, Myeloid Cells, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Quantitative Trait Loci
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
11
Publisher
Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)