📣Excited to share our paper in Nature Genetics!
https://rdcu.be/d7mo0
Do plasma proteins mediate obesity’s effect on CAD risk?
→Using two-step proteome-wide MR, domain-aware MR, epigenomics & scRNA-seq, we prioritized endotrophin, cleaved from COL6A3, as a mediator & potential therapeutic target.
A 🧵↓
https://rdcu.be/d7mo0
Do plasma proteins mediate obesity’s effect on CAD risk?
→Using two-step proteome-wide MR, domain-aware MR, epigenomics & scRNA-seq, we prioritized endotrophin, cleaved from COL6A3, as a mediator & potential therapeutic target.
A 🧵↓
Comments
• ↓Body fat → ↓endotrophin → ↓CAD risk
• Two-step proteome-wide MR identifies proteins linking risk factors to disease
• Domain-aware MR shows only C-terminal COL6A3, cleaved into endotrophin, is causal for CAD
• Supports Endotrophin as a potential CAD target
First, we used MR to evaluate the causal effect of obesity on plasma proteins to identify “BMI-driven proteins.”
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Interestingly, domain-aware MR, enabled by two aptamers targeting the C- and N-terminals of COL6A3, found that the causal effect was driven by the C-terminal, cleaved into the adipokine endotrophin.
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