Proteomic Pathways Linking Type 2 Diabetes Genetic Clusters to Cardiovascular Diseases: A Network Mendelian Randomisation Study
Authors' conclusion
This proteogenomic MR study delineates protein-mediated pathways linking cluster-stratified T2D genetic predisposition to cardiovascular risk
Study context
- Population
- Genetic data on T2D and eight genetic clusters and 12 cardiovascular diseases (CVDs) (N ≤ 1,946,349)T2D clusters GWAS
- Participants
- 2,535,601 participants
- Comparison
- Genetic liability to T2D and eight T2D genetic clusters vs 12 CVDs, with proteomic mediators
- Outcome
- Associations of T2D genetic clusters with CVDs and proteomic mediators
Methodological detailstwo-step Mendelian randomisation (MR) (mediation), inverse-variance weighted main analysis, genetic colocalisation sensitivity analysis, European-specific and Olink proteomic replication, false discovery rate (FDR) correction
- Two-step MR (mediation)
- Inverse-variance weighted main analysis
- Genetic colocalisation sensitivity analysis
- European-specific and Olink proteomic replication
- FDR correction
Main finding
As reported in the abstract
Protein signals related to obesity cluster
2739 out of 4907
Proteomic signals associated with glycemia-related clusters
≤ 13
Proportion mediated among 16 proteins supported by colocalisation (PPH4 > 0.8)
1.2% to 36.8%
Further findings
- Sensitivity and replication analyses gave similar estimates
Original publication
Proteomic Pathways Linking Type 2 Diabetes Genetic Clusters to Cardiovascular Diseases: A Network Mendelian Randomisation Study. Diabetes Obes Metab. Published 24 August 2026. doi:10.
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