Type 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes.

2.50
Hdl Handle:
http://hdl.handle.net/11287/610787
Title:
Type 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes.
Authors:
Patel, Kashyap; Oram, Richard A.; Flanagan, Sarah; De Franco, Elisa; Colclough, Kevin; Shepherd, Maggie ( 0000-0003-2660-0955 ) ; Ellard, Sian ( 0000-0002-7620-5526 ) ; Weedon, M. N.; Hattersley, Andrew T.
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 (>50(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 <5(th) T1D centile, 50-75(th) T1D centile and >75(th) T1D centile, respectively. Applying a GRS 50(th) 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 >50(th) 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.
Citation:
Type 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes. 2016 Jul;65(7):2094-9: Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
5-Apr-2016
URI:
http://hdl.handle.net/11287/610787
DOI:
10.2337/db15-1690
PubMed ID:
27207547
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=27207547
Type:
Journal Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
Diabetes/Endocrine Services; Molecular Genetics; Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPatel, Kashyapen
dc.contributor.authorOram, Richard A.en
dc.contributor.authorFlanagan, Sarahen
dc.contributor.authorDe Franco, Elisaen
dc.contributor.authorColclough, Kevinen
dc.contributor.authorShepherd, Maggieen
dc.contributor.authorEllard, Sianen
dc.contributor.authorWeedon, M. N.en
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2016-05-26T11:47:42Z-
dc.date.available2016-05-26T11:47:42Z-
dc.date.issued2016-04-05-
dc.identifier.citationType 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes. 2016 Jul;65(7):2094-9: Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid27207547-
dc.identifier.doi10.2337/db15-1690-
dc.identifier.urihttp://hdl.handle.net/11287/610787-
dc.description.abstractDistinguishing 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 (>50(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 <5(th) T1D centile, 50-75(th) T1D centile and >75(th) T1D centile, respectively. Applying a GRS 50(th) 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 >50(th) 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.en
dc.languageENG-
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=27207547en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleType 1 Diabetes Genetic Risk Score: a novel tool to discriminate monogenic and type 1 diabetes.en
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.description.fundingWellcome Trust (076113)en
dc.type.versionIn press (epub ahead of print)en

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