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

doi:10.1038/s41467-022-35663-x

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

Epidemiology

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Article number	544
Number of pages	9
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-35663-x
Publication status	Published - 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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Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic responseFinal published version, 1.91 MBLicence: CC BY

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Dekkers, K. F., Slieker, R. C., the Biobank-based Integrative Omics Study (BIOS) Consortium, Ioan-Facsinay, A., van Iterson, M., Ikram, M. A., van Greevenbroek, M. M. J., Veldink, J. H., Franke, L., Boomsma, D. I., Slagboom, P. E., Jukema, J. W., & Heijmans, B. T. (2023). Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response. Nature Communications, 14(1), Article 544. https://doi.org/10.1038/s41467-022-35663-x

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title = "Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response",

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.",

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

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: {\textcopyright} 2023, The Author(s).",

year = "2023",

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doi = "10.1038/s41467-022-35663-x",

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Dekkers, KF, Slieker, RC, the Biobank-based Integrative Omics Study (BIOS) Consortium, Ioan-Facsinay, A, van Iterson, M, Ikram, MA, van Greevenbroek, MMJ, Veldink, JH, Franke, L, Boomsma, DI, Slagboom, PE, Jukema, JW & Heijmans, BT 2023, 'Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response', Nature Communications, vol. 14, no. 1, 544. https://doi.org/10.1038/s41467-022-35663-x

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AU - Dekkers, Koen F.

AU - Slieker, Roderick C.

AU - the Biobank-based Integrative Omics Study (BIOS) Consortium

AU - Ioan-Facsinay, Andreea

AU - van Iterson, Maarten

AU - Ikram, M. Arfan

AU - van Greevenbroek, Marleen M.J.

AU - Veldink, Jan H.

AU - Franke, Lude

AU - Boomsma, Dorret I.

AU - Slagboom, P. Eline

AU - Jukema, J. Wouter

AU - Heijmans, Bastiaan T.

N1 - 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).

PY - 2023/2/1

Y1 - 2023/2/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-022-35663-x

DO - 10.1038/s41467-022-35663-x

M3 - Article

C2 - 36725846

AN - SCOPUS:85147235793

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 544

ER -

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

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