Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk.
Nat Commun
; 11(1): 3761, 2020 07 28.
Article
em En
| MEDLINE
| ID: mdl-32724101
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Desenvolvimento Infantil
/
Regulação da Expressão Gênica no Desenvolvimento
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Locos de Características Quantitativas
/
Hipersensibilidade
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Humans
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Infant
/
Newborn
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article