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

Author

Listed:
  • Qin Qin Huang

    (Baker Heart and Diabetes Institute
    University of Melbourne
    Wellcome Sanger Institute)

  • Howard H. F. Tang

    (Baker Heart and Diabetes Institute
    The University of Melbourne)

  • Shu Mei Teo

    (Baker Heart and Diabetes Institute
    University of Cambridge)

  • Danny Mok

    (The University of Western Australia)

  • Scott C. Ritchie

    (Baker Heart and Diabetes Institute
    University of Cambridge
    University of Cambridge
    University of Cambridge and Cambridge University Hospitals)

  • Artika P. Nath

    (Baker Heart and Diabetes Institute
    University of Cambridge)

  • Marta Brozynska

    (Baker Heart and Diabetes Institute
    University of Cambridge)

  • Agus Salim

    (Baker Heart and Diabetes Institute
    The University of Melbourne
    Melbourne School of Population and Global Health)

  • Andrew Bakshi

    (Monash University)

  • Barbara J. Holt

    (The University of Western Australia)

  • Chiea Chuen Khor

    (Genome Institute of Singapore, Agency for Science, Technology and Research
    Singapore Eye Research Institute
    Duke-NUS Medical School)

  • Peter D. Sly

    (The University of Queensland)

  • Patrick G. Holt

    (The University of Western Australia
    The University of Queensland)

  • Kathryn E. Holt

    (Monash University
    The London School of Hygiene and Tropical Medicine)

  • Michael Inouye

    (Baker Heart and Diabetes Institute
    University of Melbourne
    University of Cambridge
    University of Cambridge)

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.

Suggested Citation

  • Qin Qin Huang & Howard H. F. Tang & Shu Mei Teo & Danny Mok & Scott C. Ritchie & Artika P. Nath & Marta Brozynska & Agus Salim & Andrew Bakshi & Barbara J. Holt & Chiea Chuen Khor & Peter D. Sly & Pat, 2020. "Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17477-x
    DOI: 10.1038/s41467-020-17477-x
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    Cited by:

    1. Benjamin J. Schmiedel & Job Rocha & Cristian Gonzalez-Colin & Sourya Bhattacharyya & Ariel Madrigal & Christian H. Ottensmeier & Ferhat Ay & Vivek Chandra & Pandurangan Vijayanand, 2021. "COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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