Type 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes
De Franco, E
American Diabetes Association
© 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.
th 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.
ATH and SE are Wellcome Trust Senior Investigators and ATH is also supported by an NIHR Senior Investigator award. Additional support came from the University of Exeter and the NIHR Exeter Clinical Research Facility. KAP and RAO are supported by NIHR Clinical lecturer award. MNW is supported by the Wellcome Trust Institutional Support Fund (WT097835MF) and the Medical Research Council (MR/M005070/1). SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (105636/Z/14/Z). This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR or the Department of Health.
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.
2016, doi: 10.2337/db15-1690