Association of circulating metabolites and polygenic risk score with incident type 2 diabetes: a prospective community-based cohort study
Authors' conclusion
Several metabolites were found to mediate the association between PRS and incident T2DM. These findings may contribute to a better understanding of the metabolic pathways involved in genetic susceptibility to T2DM.
Study context
- Population
- Community-based participants aged ≥20 years in Japan354 T2D cases
- Participants
- 12,461 participants
- Exposure
- PRS and circulating metabolites vs incident T2D
- Outcome
- Incident T2D (non-fasting glucose ≥200 mg/dL, HbA1c ≥6.5%, or self-reported T2D treatment)
- Follow-up
- 4.3-year median
Methodological detailsgenome-wide and pathway-based polygenic risk scores, NMR metabolomics (43 metabolites), modified Poisson regression, mediation analysis
- Genome-wide and pathway-based polygenic risk scores
- NMR metabolomics (43 metabolites)
- Modified Poisson regression
- Mediation analysis
Main finding
As reported in the abstract
Higher genome-wide PRS, RR per 1-SD increment
2.09
95% CI 1.68–2.60P < 0.001
Nitrogen compound transport pathway PRS, RR per 1-SD increment
1.32
95% CI 1.03–1.70P < 0.001
Metabolites positively associated with T2D risk (glucose, 2-ketoisocaproic acid, glutamic acid, leucine, 2-aminobutyric acid, 2-hydroxybutyric acid, valine, 3-methyl-2-oxobutyric acid, alanine, 3-hydroxybutyric acid, 3-methyl-2-oxiovaleric acid, formic acid, arginine, tyrosine)
14
Metabolites (of 43) positively associated with PRS (P for linear trend < 0.05)
14
Observational data: associations, not effects.
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →