Genetic Risk and Transition Through Preclinical Stages of Type 1 Diabetes
Authors' conclusion
Genetics influence transitions through each stage of preclinical T1D, with main contributions from HLA class II. These results increase our understanding of T1D development and support incorporating the T1D GRS2 to enhance the prediction of progression through the preclinical stages of T1D.
Study context
- Population
- TrialNet participants genotyped with the TEDDY-T1DExomeChip array
- Exposure
- T1D genetic risk and transition through T1D stages
- Outcome
- Transitions between T1D stages: single confirmed autoantibody positive to stage 1, stage 1 to stage 2, stage 2 to stage 3 (clinical) T1D
Methodological detailsgenetic association analysis
- Genetic association analysis
Main finding
As reported in the abstract
Genetic risk score (GRS2), single-autoantibody positivity to stage 1 (N = 4314): HR
1.11 (1.09-1.14) (CI as printed)
GRS2, stage 1 to 2 (N = 3066): HR
1.05 (1.03-1.08) (CI as printed)
GRS2, stage 2 to 3 (N = 2045): HR
1.13 (1.09-1.17) (CI as printed)
Observational data: associations, not effects.
Further findings
GRS2 human leukocyte antigen (HLA) and HLA class II components
- Associated with all 3 transitions
HLA class I component, HLA-DR4 and HLA-DR3 haplotypes
- HLA class I and HLA-DR4 associated with single-autoantibody positivity to stage 1 and stage 2 to 3 transitions
- HLA-DR3 associated only with stage 2 to 3 transition
Original publication
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