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

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.

SUBMITTER: Huang QQ

PROVIDER: S-EPMC7387553 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Huang Qin Qin QQ Tang Howard H F HHF Teo Shu Mei SM Mok Danny D Ritchie Scott C SC Nath Artika P AP Brozynska Marta M Salim Agus A Bakshi Andrew A Holt Barbara J BJ Khor Chiea Chuen CC Sly Peter D PD Holt Patrick G PG Holt Kathryn E KE Inouye Michael M

Nature communications 20200728 1

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<sup>+</sup> 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 resp ...[more]

PMID: 32724101

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

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

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