Potential therapeutic targets for deep vein thrombosis: A proteome-wide Mendelian randomization study

Area of Science:

• Genetics
• Proteomics
• Cardiovascular Medicine

Background:

• Deep vein thrombosis (DVT) of the lower extremities poses a significant health risk.
• There is a critical need for novel drug targets for effective DVT treatment.

Purpose of the Study:

• To investigate causal associations between plasma proteins and DVT using a proteome-wide Mendelian randomization approach.
• To identify potential therapeutic targets and biomarkers for DVT screening and management.

Main Methods:

• Proteome-wide Mendelian randomization (MR) study utilizing data from 35,559 participants.
• Employed multiple analysis methods, replication analyses, mediation MR, and pathway enrichment analyses.
• Conducted druggability evaluation and phenome-wide MR analysis for drug development assessment.

Main Results:

• Identified 12 plasma proteins with significant causal associations with DVT.
• MAP1LC3A, LRP12, VWF, F2, SYK, F11, KLKB1, and LRP4 showed increased DVT risk; SERPINE2, XXYLT1, PMVK, and RGS18 demonstrated protective effects.
• LRP12 and F11 provided the strongest evidence; identified F2-Triglycerides-DVT and MAP1LC3A-eGFR-DVT pathways; several proteins (F11, F2, KLKB1, SYK, VWF) are already drug targets.

Conclusions:

• Identified 12 novel protein targets associated with lower extremity DVT.
• These findings provide promising avenues for developing new therapeutic agents and biomarkers for DVT.
• The study highlights the potential of LRP12, F11, F2, KLKB1, SYK, and VWF in DVT drug development and screening.