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Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes
Dina Mansour Aly1, Om Prakash Dwivedi2, Rashmi B Prasad1
1Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Nature Genetics
|November 5, 2021
Summary
Type 2 diabetes subtypes show distinct genetic drivers, impacting disease progression and complication risks. Genetic analysis reveals unique associations for severe insulin resistance and mild obesity-related forms, suggesting different causes.
Area of Science:
- Genetics
- Endocrinology
- Metabolic Diseases
Background:
- Type 2 diabetes (T2D) is heterogeneous, with five established subtypes.
- Subtypes exhibit varying disease progression and complication risks.
- Underlying etiological differences between T2D subtypes remain largely unknown.
Purpose of the Study:
- To investigate the distinct genetic drivers of T2D subtypes.
- To compare the genetic underpinnings of different T2D classifications.
Main Methods:
- Genome-wide association studies (GWAS) and genetic risk score (GRS) analyses were employed.
- Data from the Swedish ANDIS study and Finnish DIREVA/Botnia studies were utilized for discovery and replication.
- Subtypes were analyzed for associations with family history and GRS for diabetes-related traits.
Main Results:
- T2D subtypes demonstrated differences in family history and GRS associations.
- Severe insulin-resistant T2D was uniquely linked to GRS for fasting insulin.
- A specific SNP (rs10824307) near LRMDA was associated with mild obesity-related T2D.
Conclusions:
- The identified T2D subtypes possess partially distinct genetic backgrounds.
- These genetic differences suggest unique etiological pathways for T2D subtypes.
- Findings contribute to understanding the heterogeneity of Type 2 diabetes.
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