TY - JOUR
T1 - Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response
AU - Dekkers, Koen F.
AU - Slieker, Roderick C.
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.
AU - BIOS Consortium
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.
KW - GENOME-WIDE ASSOCIATION
KW - MENDELIAN RANDOMIZATION
KW - INSIGHTS
KW - PLASMA
KW - INFLAMMATION
KW - METAANALYSIS
KW - CHOLESTEROL
KW - SURVIVAL
KW - DISEASE
KW - OBESITY
U2 - 10.1038/s41467-022-35663-x
DO - 10.1038/s41467-022-35663-x
M3 - Article
C2 - 36725846
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 544
ER -