Integrative metabolomics and genomics reveal molecular signatures for type 2 diabetes and its cardiovascular complications
Authors' conclusion
Our study provides novel insights into the metabolic underpinnings of T2D and its cardiovascular complications, emphasizing the role of urea cycle-related metabolites in disease risk and progression. These findings advance our understanding of circulating metabolites in the etiology of T2D, offering potential biomarkers and therapeutic targets for future research.
Study context
- Population
- Chinese participants from the Zhejiang Metabolic Syndrome Cohort (ZMSC); 1912 metabolites profiled
- Participants
- 1,180 participants
- Outcome
- T2D-related metabolites and potential causal metabolite-T2D associations
Methodological detailsmetabolome-wide genome-wide association study (GWAS), two-sample Mendelian randomization, cross-ancestry (European) Mendelian randomization (MR), multi-omics integration
- Metabolome-wide GWAS
- Two-sample Mendelian randomization
- Cross-ancestry (European) MR
- Multi-omics integration
Main finding
As reported in the abstract
Metabolites associated with T2D, supported by metabolome analysis and genetic-informed causal inference
6
Potential protective factors: PC [O-16:0/0:0] and its derivative LPC [O-16:0]
2
Potential risk factors: [R]-2-hydroxybutyric acid, 2-methyllactic acid, eplerenone, rauwolscine
4
Observational data: associations, not effects.
Further findings
Cross-ancestry shared potential causal metabolites
- Shared potential causal metabolites; potential protective role of creatine for T2D
- 4
Multi-omics regulatory path
- Genetic variant near CPS1 (urea cycle-related mitochondrial enzyme) influences serum creatine levels, subsequently modulating T2D risk
Cardiovascular complications of T2D
- Urea cycle-related metabolites significantly influencing cardiovascular complications of T2D (MR)
- 9
Original publication
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