A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults

2.50
Hdl Handle:
http://hdl.handle.net/11287/593968
Title:
A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults
Authors:
Oram, Richard A.; Patel, K.; Hill, Anita; Shields, Beverley M; McDonald, Timothy J. ( 0000-0003-3559-6660 ) ; Jones, Angus; Hattersley, Andrew T.; Weedon, M. N.
Abstract:
OBJECTIVE: With rising obesity, it is becoming increasingly difficult to distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D) in young adults. There has been substantial recent progress in identifying the contribution of common genetic variants to T1D and T2D. We aimed to determine whether a score generated from common genetic variants could be used to discriminate between T1D and T2D, and also to predict severe insulin deficiency in young adults with diabetes. RESEARCH DESIGN AND METHODS: We developed genetic risk scores (GRSs) from published T1D- and T2D-associated variants. We first tested whether the scores could distinguish clinically defined T1D and T2D from the Wellcome Trust Case Control Consortium (WTCCC, n = 3,887). We then assessed if the T1D GRS correctly classified young adults (diagnosed at 20-40 years of age, the age group with the most diagnostic difficulty in clinical practice; n = 223) who progressed to severe insulin deficiency <3 years from diagnosis. RESULTS: In the WTCCC, the T1D GRS, based on 30 T1D-associated risk variants, was highly discriminative of T1D and T2D (area under the curve [AUC] 0.88 [95% CI 0.87-0.89]; P < 0.0001), and the T2D GRS added little discrimination (AUC 0.89). A T1D GRS >0.280 (>50th centile in those with T1D) is indicative of T1D (50% sensitivity, 95% specificity). A low T1D GRS (<0.234, <5th centile T1D) is indicative of T2D (53% sensitivity, 95% specificity). Most discriminative ability was obtained from just nine single nucleotide polymorphisms (AUC 0.87). In young adults with diabetes, T1D GRS alone predicted progression to insulin deficiency (AUC 0.87 [95% CI 0.82-0.92]; P < 0.0001). T1D GRS, autoantibody status, and clinical features were independent and additive predictors of severe insulin deficiency (combined AUC 0.96 [95% CI 0.94-0.99]; P < 0.0001). CONCLUSIONS: A T1D GRS can accurately identify young adults with diabetes who will require insulin treatment. This will be an important addition to correctly classifying individuals with diabetes when clinical features and autoimmune markers are equivocal.
Citation:
Diabetes Care. 2016 Mar;39(3):337-44
Publisher:
Diabetes Care
Journal:
Diabetes care
Issue Date:
17-Nov-2015
URI:
http://hdl.handle.net/11287/593968
DOI:
10.2337/dc15-1111
PubMed ID:
26577414
Additional Links:
http://care.diabetesjournals.org/content/early/2015/10/30/dc15-1111.long
Type:
Journal Article
Language:
Eng
ISSN:
1935-5548
Appears in Collections:
2015 RD&E publications; Diabetes/Endocrine Services

Full metadata record

DC FieldValue Language
dc.contributor.authorOram, Richard A.en
dc.contributor.authorPatel, K.en
dc.contributor.authorHill, Anitaen
dc.contributor.authorShields, Beverley Men
dc.contributor.authorMcDonald, Timothy J.en
dc.contributor.authorJones, Angusen
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorWeedon, M. N.en
dc.date.accessioned2016-01-19T12:38:05Zen
dc.date.available2016-01-19T12:38:05Zen
dc.date.issued2015-11-17en
dc.identifier.citationDiabetes Care. 2016 Mar;39(3):337-44en
dc.identifier.issn1935-5548en
dc.identifier.pmid26577414en
dc.identifier.doi10.2337/dc15-1111en
dc.identifier.urihttp://hdl.handle.net/11287/593968en
dc.description.abstractOBJECTIVE: With rising obesity, it is becoming increasingly difficult to distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D) in young adults. There has been substantial recent progress in identifying the contribution of common genetic variants to T1D and T2D. We aimed to determine whether a score generated from common genetic variants could be used to discriminate between T1D and T2D, and also to predict severe insulin deficiency in young adults with diabetes. RESEARCH DESIGN AND METHODS: We developed genetic risk scores (GRSs) from published T1D- and T2D-associated variants. We first tested whether the scores could distinguish clinically defined T1D and T2D from the Wellcome Trust Case Control Consortium (WTCCC, n = 3,887). We then assessed if the T1D GRS correctly classified young adults (diagnosed at 20-40 years of age, the age group with the most diagnostic difficulty in clinical practice; n = 223) who progressed to severe insulin deficiency <3 years from diagnosis. RESULTS: In the WTCCC, the T1D GRS, based on 30 T1D-associated risk variants, was highly discriminative of T1D and T2D (area under the curve [AUC] 0.88 [95% CI 0.87-0.89]; P < 0.0001), and the T2D GRS added little discrimination (AUC 0.89). A T1D GRS >0.280 (>50th centile in those with T1D) is indicative of T1D (50% sensitivity, 95% specificity). A low T1D GRS (<0.234, <5th centile T1D) is indicative of T2D (53% sensitivity, 95% specificity). Most discriminative ability was obtained from just nine single nucleotide polymorphisms (AUC 0.87). In young adults with diabetes, T1D GRS alone predicted progression to insulin deficiency (AUC 0.87 [95% CI 0.82-0.92]; P < 0.0001). T1D GRS, autoantibody status, and clinical features were independent and additive predictors of severe insulin deficiency (combined AUC 0.96 [95% CI 0.94-0.99]; P < 0.0001). CONCLUSIONS: A T1D GRS can accurately identify young adults with diabetes who will require insulin treatment. This will be an important addition to correctly classifying individuals with diabetes when clinical features and autoimmune markers are equivocal.en
dc.language.isoEngen
dc.publisherDiabetes Careen
dc.relation.urlhttp://care.diabetesjournals.org/content/early/2015/10/30/dc15-1111.longen
dc.titleA Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adultsen
dc.typeJournal Articleen
dc.identifier.journalDiabetes careen

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.