A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults
Article Figures & Tables
Figures
- Figure 1
The ability of a T1D risk score to discriminate between clinically defined T1D and T2D diabetes in the WTCCC study. A: A dot plot of T1D GRSs by T1D and T2D status. The width of the blue bars indicates frequency, and the red line is the median. B: ROC curve of the T1D, T2D, and combined GRSs for discriminating between T1D and T2D. The red line represents the T2D GRS, the blue line represents the T1D GRS, and the green line represents the T1D plus T2D GRS. The respective ROC AUCs are as follows: 0.64, 0.88, and 0.89.
- Figure 2
The ability of a T1D GRS to discriminate between severe insulin deficiency and noninsulin deficiency in young adults with diabetes. A dot plot of T1D GRS by insulin deficiency status is shown. The width of the blue bars represents frequency, and the red line represents the median.
- Figure 3
A series of ROC analyses demonstrating that the T1D GRS is an additive and independent predictor of insulin deficiency in young adults with diabetes when compared with known biomarker and clinical discriminators. AAD, age at diagnosis; ABS, autoantibody status for GAD and IA-2; ALL, T1D GRS, BMI, age at diagnosis, and autoantibodies as predictors. The combination of T1D GRS, autoantibodies, BMI, and age at diagnosis provides a highly discriminative test.
- Figure 4
The incremental increase in the discriminatory power of the T1D GRS as more SNPs are added in. After ordering by published effect size, this graph shows the increasing AUC for increasing numbers of SNPs. After nine SNPs, there is no significantly increased discriminatory power to adding the next SNP. The x-axis starts at two SNPs that define the DR3/DR4-DQ8 high-risk haplotypes. The gray bars represent the upper and lower 95% CIs for the AUC estimate.
Tables
- Table 1
Clinical characteristics of local cohort diagnosed between 20 and 40 years of age
Severely insulin deficient (N = 46) Not severely insulin deficient (N = 177) P for difference Males (%) 59 43 0.23 Clinical diagnosis of T1D/T2D 42/4 9/164 <0.0001 Age at study (years) 53.9 (12.1) 48.3 (9.7) 0.001 Age at diagnosis (years) 26.0 (5.2) 33.4 (4.2) <0.0001 Duration of diabetes (years) 27.9 (12.5) 14.9 (9.1) <0.0001 BMI 26.5 (4.3) 37.2 (9.2) <0.0001 T1D autoantibodies (positive GAD or IA-2/total) 15/24 9/156 <0.0001 Insulin treatment at diagnosis, n (%) 38 (83) 8 (5) <0.0001 Insulin treatment at recruitment, n (%) 46 (100) 84 (47) <0.0001 Time to insulin (months) Median (IQR) 0 (0, 0) 96 (36, 134) <0.0001 Data are reported as mean (SD), unless otherwise indicated. BMI and antibodies (GAD and IA-2) were measured at study recruitment.
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