Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India

Abstract

Type 1 diabetes (T1D) is a significant problem in Indians and misclassification of T1D and type 2 diabetes (T2D) is a particular problem in young adults in this population due to the high prevalence of early onset T2D at lower BMI. We have previously shown a genetic risk score (GRS) can be used to discriminate T1D from T2D in Europeans. We aimed to test the ability of a T1D GRS to discriminate T1D from T2D and controls in Indians. We studied subjects from Pune, India of Indo-European ancestry; T1D (n = 262 clinically defined, 200 autoantibody positive), T2D (n = 345) and controls (n = 324). We used the 9 SNP T1D GRS generated in Europeans and assessed its ability to discriminate T1D from T2D and controls in Indians. We compared Indians with Europeans from the Wellcome Trust Case Control Consortium study; T1D (n = 1963), T2D (n = 1924) and controls (n = 2938). The T1D GRS was discriminative of T1D from T2D in Indians but slightly less than in Europeans (ROC AUC 0.84 v 0.87, p < 0.0001). HLA SNPs contributed the majority of the discriminative power in Indians. A T1D GRS using SNPs defined in Europeans is discriminative of T1D from T2D and controls in Indians. As with Europeans, the T1D GRS may be useful for classifying diabetes in Indians.

Figure 1

Comparison of the ability of a 9 SNP GRS to discriminate between T1D and T2D in Indians and Europeans. (A) Dotplot of 9 SNP T1D GRS in T1D, T2D and controls in Indians and Europeans. The width of the blue bars indicates frequency and the red line indicates the median. (B) ROC curves showing the power of the 9 SNP T1D GRS to discriminate between T1D and T2D in Indians (blue: AUC [95% CI] 0.84 [0.80–0.87]) and Europeans (red: AUC [95% CI] 0.87 [0.86–0.88]), P < 0.001.

Figure 2

Comparison of odds ratios for DR3/DR4 haplotype combinations between Indians (blue circle) and Europeans (red circle). Bars show 95% confidence intervals.