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Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response

Author

Listed:
  • Koen F. Dekkers

    (Leiden University Medical Center)

  • Roderick C. Slieker

    (Leiden University Medical Center
    Amsterdam UMC, VUmc)

  • Andreea Ioan-Facsinay

    (Leiden University Medical Center)

  • Maarten Iterson

    (Leiden University Medical Center)

  • M. Arfan Ikram

    (Erasmus MC)

  • Marleen M. J. Greevenbroek

    (Maastricht University Medical Center)

  • Jan H. Veldink

    (Utrecht University)

  • Lude Franke

    (University Medical Center Groningen)

  • Dorret I. Boomsma

    (Vrije Universiteit Amsterdam)

  • P. Eline Slagboom

    (Leiden University Medical Center)

  • J. Wouter Jukema

    (Leiden University Medical Center
    Netherlands Heart Institute)

  • Bastiaan T. Heijmans

    (Leiden University Medical Center)

Abstract

Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease.

Suggested Citation

  • Koen F. Dekkers & Roderick C. Slieker & Andreea Ioan-Facsinay & Maarten Iterson & M. Arfan Ikram & Marleen M. J. Greevenbroek & Jan H. Veldink & Lude Franke & Dorret I. Boomsma & P. Eline Slagboom & J, 2023. "Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35663-x
    DOI: 10.1038/s41467-022-35663-x
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