Genetic Risk Factors for Kidney Function in Individuals with Type 1 Diabetes.

KEY POINTS: Previous research has identified polygenic risk scores that are associated with low eGFR and albuminuria in the general population. We observed that these eGFR and albuminuria polygenic risk scores were associated with eGFR and albuminuria, respectively, in type 1 diabetes. Associations were independent of glycemic control and suggest shared genetic kidney risk factors between type 1 diabetes and the general population. BACKGROUND: Genetic risk factors underlying kidney disease in type 1 diabetes (T1D) remain poorly understood. We examined whether previously established polygenic risk scores (PRS) for eGFR and albuminuria are associated with these measures in adults with T1D in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study. METHODS: We applied eGFR and albuminuria PRS derived in general population cohorts to 1304 DCCT/Epidemiology of Diabetes Interventions and Complications participants with genome-wide genotyping. We tested PRS associations with eGFR and urine albumin excretion rate (AER) as well as incident eGFR RESULTS: At DCCT baseline, participants had a mean age of 27 years; 53% were male. 49% of participants were randomized to intensive versus conventional glucose-lowering therapy. Participants were followed for median of (first-third quartiles) 35 (33-37) years. The eGFR PRS was significantly associated with continuous eGFR (per one SD higher PRS 2.72 ml/min per 1.73 m 2 higher [95% confidence interval (CI), 2.05 to 3.40]) and incident eGFR CONCLUSIONS: PRS associated with eGFR and albuminuria in the general population were associated with corresponding measures in adults with T1D. The results suggest shared genetic risk factors for kidney disease between T1D and the general population but different genetic risk factors for albuminuria and eGFR in T1D. CLINICAL TRIALS REGISTRATION NUMBERS: NCT00360893 , NCT00360815 .