Pulmonary vascular disease & thromboembolism
Novel Plasma Proteomic Markers and Risk of Venous Thromboembolism
Authors' conclusion
We identified several novel plasma proteins for VTE that reflect biological processes outside established VTE pathophysiology, including extracellular matrix regulation, immunity, immune-vascular endothelium interactions, and vascular senescence.
Study context
- Population
- Participants of ARIC, CHS, MESA and HUNT cohorts followed for incident noncancer venous thromboembolism (VTE) (max 10 to 29 years)
- Participants
- 20,737 participants1,371 incident noncancer VTEs
- Outcome
- Incident noncancer VTE; association of baseline plasma proteins (≈5000 to 7000) with VTE risk
- Follow-up
- Maximum of 10 to 29 years
Methodological details4 longitudinal cohorts (ARIC, CHS, MESA, HUNT), discovery meta-analysis with replication in HUNT, external replication in UK Biobank (Olink), aptamer-based proteomics (SomaScan), Cox proportional hazards regression, Mendelian randomization
- 4 longitudinal cohorts (ARIC, CHS, MESA, HUNT)
- Discovery meta-analysis with replication in HUNT
- External replication in UK Biobank (Olink)
- Aptamer-based proteomics (SomaScan)
- Cox proportional hazards regression
- Mendelian randomization
Main finding
As reported in the abstract
Proteins exceeding FDR-adjusted P<0.05 (unadjusted P<6.5×10-4) in discovery meta-analysis and replicated in HUNT at unadjusted P<0.05
23
Proteins new to VTE
15
New proteins exceeding Bonferroni threshold in HUNT (transgelin, SVEP1, TIMP4)
3
Observational data: associations, not effects.
Further findings
External replication in UK Biobank (Olink), 783 incident noncancer VTEs among 39 097 participants
- Top VTE proteins available on UKB Olink panel
- 16
- Replicated in UKB after Bonferroni correction
- 11
Mendelian randomization (MR) analysis of the 15 new proteins
- Significant evidence for possible causal role of TIMD4
- Bonferroni-corrected P<0.05
- Suggestive evidence for TIMP4 and CST3 (cystatin-c)
- unadjusted P<0.05
- MR direction opposite to proteomics for TIMP4 and TIMD4, consistent for CST3
Original publication
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