Genome‐Wide Association Analyses Identify Distinct Genetic Architectures for Extreme Early‐Onset and Late‐Onset T2D
Authors' conclusion
Extreme AAO-defined T2D subtypes exhibit partially distinct genetic architectures, highlighting AAO as an important dimension of T2D heterogeneity
Study context
- Population
- European-ancestry participants from the UK BiobankEuropean ancestry
- Participants
- 74,795 participants
- Comparison
- Early-onset T2D vs late-onset T2D
- Outcome
- SNP-based heritability
Methodological detailsUK Biobank, SNP-based heritability, genetic correlation (LDSC), Mendelian randomization, polygenic risk scores, phenome-wide association studies (PheWAS), single-cell transcriptomics of human pancreatic tissue
- UK Biobank
- SNP-based heritability
- Genetic correlation (LDSC)
- Mendelian randomization
- Polygenic risk scores
- PheWAS
- Single-cell transcriptomics of human pancreatic tissue
Performance
As reported in the abstract
Further findings
Genetic overlap (LDSC) and Mendelian randomization (MR) relationships
- Early-onset T2D (eoT2D) exhibited broader genetic overlap with cardiometabolic traits, whereas late-onset T2D (loT2D) showed stronger relationships with traditional metabolic risk factors
Subtype-specific polygenic risk scores (PRSs)
- Subtype-specific PRSs improved risk discrimination beyond conventional covariates; clinical utility warrants further evaluation
Original publication
Genome‐Wide Association Analyses Identify Distinct Genetic Architectures for Extreme Early‐Onset and Late‐Onset T2D. Diabetes Obes Metab. Published 8 September 2026. doi:10.
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