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Diabetes. 2016 Jul;65(7):2094-2099. doi: 10.2337/db15-1690. Epub 2016 Apr 5.

Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes.

Author information

1
Institute for Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, UK.
2
National Institute for Health Research, Exeter Clinical Research Facility, Barrack Road, Exeter EX2 5DW, UK.
3
Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, Barrack Road, Exeter EX2 5DW, UK.
#
Contributed equally

Abstract

Distinguishing patients with monogenic diabetes from those with type 1 diabetes (T1D) is important for correct diagnosis, treatment, and selection of 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 maturity-onset diabetes of young (MODY) (n = 805) and T1D (n = 1,963) (receiver operating characteristic area under the curve 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 of 242 white European patients with neonatal diabetes (NDM) who had been tested for all known NDM genes. Monogenic NDM was confirmed in 90, 59, and 8% of patients with GRS <5th T1D centile, 50-75th T1D centile, and >75th T1D centile, respectively. Applying a GRS 50th T1D centile cutoff 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 and had less syndromic presentation but additional autoimmune features compared with those with proven monogenic NDM. The T1D-GRS is a novel tool to improve the use of biomarkers in the discrimination of monogenic diabetes from T1D.

PMID:
27207547
PMCID:
PMC4920219
DOI:
10.2337/db15-1690
[Indexed for MEDLINE]
Free PMC Article

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