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

Koen F. Dekkers, Roderick C. Slieker, the Biobank-based Integrative Omics Study (BIOS) Consortium, Andreea Ioan-Facsinay, Maarten van Iterson, M. Arfan Ikram, Marleen M.J. van Greevenbroek, Jan H. Veldink, Lude Franke, Dorret I. Boomsma, P. Eline Slagboom, J. Wouter Jukema, Bastiaan T. Heijmans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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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.

Original languageEnglish
Article number544
Number of pages9
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 1 Feb 2023

Bibliographical note

Funding Information:
This research was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO, numbers 184.021.007 and 184.033.111). We acknowledge the support from the Netherlands CardioVascular Research Initiative (the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences) for the GENIUS project Generating the best evidence-based pharmaceutical targets for atherosclerosis (CVON2011-19, CVON2017-20). This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative.

Publisher Copyright:
© 2023, The Author(s).

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