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

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. Wouter Jukema and Bastiaan T. Heijmans ()
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Koen F. Dekkers: Leiden University Medical Center
Roderick C. Slieker: Leiden University Medical Center
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
Bastiaan T. Heijmans: Leiden University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-022-35663-x

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