Journal article

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

Qin Qin Huang, Howard HF 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, Patrick G Holt, Kathryn E Holt, Michael Inouye

Nature Communications | NATURE RESEARCH | Published : 2020

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 ci..

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Grants

Awarded by NHMRC of Australia


Awarded by UK Medical Research Council


Awarded by British Heart Foundation


Funding Acknowledgements

We thank the participants, their parents, and project staff of the Childhood Asthma Study. This research was supported by the NHMRC of Australia (project grant no. 1049539 to M.I. and K.E.H., Fellowships 1061409 to K.E.H., and 1061435 to M.I.). This research was supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. This research was supported in part by the Victorian Government's Operational Infrastructure Support Program and the UK National Institute of Health Research. M.I. and S.C.R. are funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. K.E.H. is supported by a Senior Medical Research Fellowship from the Viertel Foundation of Australia. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.