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Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes

Author

Listed:
  • Eamon Fitzgerald

    (McGill University
    McGill University
    McGill University)

  • Mojun Shen

    (Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research)

  • Hannah Ee Juen Yong

    (Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research)

  • Zihan Wang

    (McGill University)

  • Irina Pokhvisneva

    (McGill University)

  • Sachin Patel

    (McGill University)

  • Nicholas O’Toole

    (McGill University
    McGill University
    McGill University)

  • Shiao-Yng Chan

    (Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research
    National University of Singapore)

  • Yap Seng Chong

    (Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research
    National University of Singapore)

  • Helen Chen

    (KK Women’s and Children’s Hospital
    Duke-National University of Singapore)

  • Peter D. Gluckman

    (Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research
    The University of Auckland)

  • Jerry Chan

    (KK Women’s and Children’s Hospital
    Duke-National University of Singapore)

  • Patrick Kia Ming Lee

    (Brain – Body Initiative, Agency for Science, Technology & Research)

  • Michael J. Meaney

    (McGill University
    McGill University
    Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research
    National University of Singapore)

Abstract

Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.

Suggested Citation

  • Eamon Fitzgerald & Mojun Shen & Hannah Ee Juen Yong & Zihan Wang & Irina Pokhvisneva & Sachin Patel & Nicholas O’Toole & Shiao-Yng Chan & Yap Seng Chong & Helen Chen & Peter D. Gluckman & Jerry Chan &, 2023. "Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42300-8
    DOI: 10.1038/s41467-023-42300-8
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    References listed on IDEAS

    as
    1. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    2. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    3. Gibran Hemani & Kate Tilling & George Davey Smith, 2017. "Orienting the causal relationship between imprecisely measured traits using GWAS summary data," PLOS Genetics, Public Library of Science, vol. 13(11), pages 1-22, November.
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