Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes
| العنوان: | Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes |
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| المؤلفون: | K Colclough, E. De Franco, Sian Ellard, Andrew T. Hattersley, Maggie Shepherd, Sarah E. Flanagan, Michael N. Weedon, Kashyap A. Patel, Richard A. Oram |
| المصدر: | Diabetes. 65:2094-2099 |
| بيانات النشر: | American Diabetes Association, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Adolescent, Genotype, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Article, Diagnosis, Differential, Young Adult, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Young adult, Type 1 diabetes, Receiver operating characteristic, business.industry, fungi, Area under the curve, nutritional and metabolic diseases, medicine.disease, 3. Good health, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Mutation, Etiology, Female, Differential diagnosis, business |
| الوصف: | 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 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. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d201743d9dd6338143e3a64851bae2cfTest https://doi.org/10.2337/db15-1690Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d201743d9dd6338143e3a64851bae2cf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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