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Genetic Risk Factors for Kidney Function in Individuals with Type 1 Diabetes
Christine P Limonte1,2, Xiaoyu Gao3, Delnaz Roshandel4
1Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
Summary
Polygenic risk scores (PRS) for kidney function and albuminuria in the general population are associated with kidney measures in type 1 diabetes (T1D) patients. This suggests shared genetic factors for kidney disease between T1D and the general population.
Area of Science:
- Nephrology
- Genetics
- Endocrinology
Background:
- Kidney disease in type 1 diabetes (T1D) has complex genetic underpinnings.
- Understanding these genetic factors is crucial for predicting and managing diabetic kidney disease.
Purpose of the Study:
- To investigate if polygenic risk scores (PRS) for estimated glomerular filtration rate (eGFR) and albuminuria, established in the general population, are associated with kidney outcomes in adults with T1D.
- To explore shared and distinct genetic risk factors for kidney disease in T1D.
Main Methods:
- Applied eGFR and albuminuria PRS from general population cohorts to 1,304 participants in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study.
- Assessed PRS associations with continuous eGFR, albuminuria (urine albumin excretion rate - AER), and incident kidney outcomes (eGFR <60ml/min/1.73m2, AER >30mg/24h, AER >300mg/24h).
- Examined the association of rs55703767 in COL4A3 with kidney outcomes in T1D.
Main Results:
- The eGFR PRS was significantly associated with higher eGFR and reduced risk of incident eGFR <60ml/min/1.73m2.
- The albuminuria PRS was significantly associated with an increased risk of incident AER >30mg/24h.
- rs55703767 was associated with lower incident macroalbuminuria, particularly in the conventional therapy group.
Conclusions:
- Established PRS for eGFR and albuminuria in the general population are relevant to kidney measures in adults with T1D.
- These findings suggest both shared genetic risk factors for kidney disease between T1D and the general population, and distinct genetic influences on eGFR and albuminuria within T1D.
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