Network Mendelian randomisation analysis deciphers protein pathways linking type 2 diabetes and gastrointestinal disease
Authors' conclusion
The study identified some proteins mediating T2D-GI disease associations, which provided biological insights into the underlying pathways.
Study context
- Population
- Summary-level genetic data: T2D genome-wide meta-analysis; plasma protein GWAS (deCODE, UKB-PPP, Fenland); 10 gastrointestinal (GI) diseases from UK Biobank and FinnGen
- Outcome
- Proteins mediating T2D–GI disease associations
Methodological detailscolocalisation analyses, discovery (deCODE) and replication (UKB-PPP, Fenland) protein datasets, druggability assessments across four databases
- Colocalisation analyses
- Discovery (deCODE) and replication (UKB-PPP, Fenland) protein datasets
- Druggability assessments across four databases
Main finding
As reported in the abstract
- Proteins associated with genetic liability to T2D (discovery, after multiple testing corrections); all replicated at nominal significance
- 69
- T2D-associated proteins whose genetically predicted levels were associated with ≥1 GI disease
- 9
- SULT2A1 and cholelithiasis, OR
- 1.98 (95% CI 1.80-2.18)
- ADH1B and cirrhosis, OR
- 2.05 (95% CI 1.43-2.94)
- SULT2A1–cholelithiasis colocalisation PH4
- 0.996
- ADH1B–cirrhosis colocalisation PH4
- 0.931
- Mediation proportion, SULT2A1 (T2D→cholelithiasis)
- 72.8% (95% CI 45.7-99.9)
- Mediation proportion, ADH1B (T2D→cirrhosis)
- 42.9% (95% CI 15.5-70.4)
Original publication
Network Mendelian randomisation analysis deciphers protein pathways linking type 2 diabetes and gastrointestinal disease. Diabetes Obes Metab. Published 26 November 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →