TY - JOUR
T1 - C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
AU - Lepik, Kaido
AU - Annilo, Tarmo
AU - Kukuškina, Viktorija
AU - Kisand, Kai
AU - Kutalik, Zoltán
AU - Peterson, Pärt
AU - Peterson, Hedi
AU - eQTLGen Consortium
AU - Penninx, BWJH
AU - Jansen, R
AU - Boomsma, D.I.
AU - Nivard, M.G.
AU - van Dongen, J.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.
AB - Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85030467275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030467275&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pcbi.1005766
DO - https://doi.org/10.1371/journal.pcbi.1005766
M3 - Article
C2 - 28922377
SN - 1553-734X
VL - 13
SP - e1005766
JO - PLoS computational biology
JF - PLoS computational biology
IS - 9
M1 - e1005766
ER -
