Population Prevalence, Penetrance, and Mortality for Genetically Confirmed Maturity-onset Diabetes of the Young (MODY)
Authors' conclusion
This large-scale genotype-first study provides novel insights into MODY in the population. These findings have broad implications for genetic counseling, personalized treatment strategies, and healthcare resource allocation.
Study context
- Population
- UK Biobank participants with exome sequencing and clinical data; pathogenic variants in 10 established MODY genes
- Participants
- 454,275 participants
- Outcome
- Population prevalence, age-dependent diabetes penetrance and all-cause mortality of MODY variants
- Follow-up
- Mean 13.4 years
Methodological detailsgenotype-first approach, exome sequencing
- Genotype-first approach
- Exome sequencing
Main finding
As reported in the abstract
Prevalence of pathogenic MODY variants
Pathogenic MODY variant carriers
1 in 1052 individuals
Share of diabetes cases diagnosed before age 40
1.48%
GCK variants (most frequent)
1 in 2787
Observational data: associations, not effects.
Further findings
Penetrance and mortality, GCK variants
- Mean HbA1c higher
- 8.8 mmol/mol
- Prediabetes or diabetes
- 94.5%
- No significant association with all-cause mortality
- P = 0.09
Penetrance and mortality, other MODY genes
- Diabetes by age 40
- 12%
- Diabetes by age 60
- 31.6%
- No increase in all-cause mortality
- P = 0.89
Penetrance by genetic etiology
- Highest penetrance with HNF1A; lowest with PDX1, NEUROD1 and RFX6
Modifiers of penetrance
- Parental history of diabetes, HR
- 2.54
- Polygenic risk for T2D, HR
- 1.52
- P
- P < 3.9 × 10-3
Original publication
Population Prevalence, Penetrance, and Mortality for Genetically Confirmed MODY. J Clin Endocrinol Metab. Published 1 November 2025. doi:10.
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