Prevention & lipidsResearch article
Proteogenomic Data Integration Reveals CXCL10 as a Potentially Downstream Causal Mediator for IL-6 Signaling on Atherosclerosis
- Mendelian randomisation study
- mediation Mendelian randomisation
- proteogenomic data integration
Authors' conclusion
Integrating multiomics data, we found a proteomic signature of IL-6 signaling activation and mediators of its effects on cardiovascular disease.
Study context
- Population
- Genetic data from 522,681 individuals; INTERVAL cohort proteomics; population-based study; human atherosclerotic lesion samplesINTERVAL n=3301
- Participants
- 522,681 participants
- Comparison
- Genetically proxied IL-6R inhibition and its proteomic mediators
Main finding
As reported in the abstract
Significant effects of genetically proxied IL-6 signaling on circulating proteins (cytokine production/regulation, immune cell recruitment/differentiation)
70
Genetically proxied CXCL10 levels associated with risk of CAD, large artery atherosclerotic stroke and PAD; share of effects of genetically downregulated IL-6 signaling mediated by decreases in CXCL10
up to 67%
Further findings
Midlife circulating CXCL10 and incident CV events (population-based study, n=1704) · 20 years
- Higher midlife CXCL10 associated with a larger number of CV events
CXCL10 expression in human atherosclerotic lesions
- Higher expression correlated with a larger lipid core and a transcriptomic profile of immune cell infiltration, adaptive immune activation and cytokine signaling
Original publication
Summarised from the published abstract; every number is checked against it