Abstract
Distinguishing patients with monogenic diabetes from Type 1 diabetes (T1D) is important for correct diagnosis, treatment and to select patients for gene discovery studies. We assessed whether a T1D genetic risk score (T1D-GRS) generated from T1D-associated common genetic variants provides a novel way to discriminate monogenic diabetes from T1D. The T1D-GRS was highly discriminative of proven MODY (n=805) and T1D (n=1963) (ROC-AUC=0.87). A T1D-GRS of >0.280 (>50th T1D centile) was indicative of T1D (94% specificity, 50% sensitivity). We then analyzed the T1D-GRS in 242 White-European patients with neonatal diabetes (NDM) who had been tested for all known neonatal diabetes genes. Monogenic NDM was confirmed in 90%, 59% and 8% in patients with GRS <5th T1D centile, 50-75th T1D centile and >75th T1D centile, respectively. Applying a GRS 50th T1D centile cut-off in 48 NDM patients with no known genetic cause, identified those most likely to have a novel monogenic etiology by highlighting patients with probable early-onset T1D (GRS >50th T1D centile) who were diagnosed later, had less syndromic presentation but had additional autoimmune features compared to proven monogenic NDM. The T1D-GRS is a novel tool to improve the use of biomarkers in the discrimination of monogenic diabetes from T1D.
- Received December 10, 2015.
- Accepted March 28, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.