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Sixty-Five Common Genetic Variants and Prediction of Type 2 Diabetes

Talmud, Philippa J and Cooper, Jackie A and Morris, Richard W and Dudbridge, Frank and Shah, Tina and Engmann, Jorgen and Dale, Caroline and White, Jon and McLachlan, Stela and Zabaneh, Delilah and Wong, Andrew and Ong, Ken K and Gaunt, Tom and Holmes, Michael V and Lawlor, Debbie A and Richards, Marcus and Hardy, Rebecca and Kuh, Diana and Wareham, Nicholas and Langenberg, Claudia and Ben-Shlomo, Yoav and Wannamethee, S Goya and Strachan, Mark WJ and Kumari, Meena and Whittaker, John C and Drenos, Fotios and Kivimaki, Mika and Hingorani, Aroon D and Price, Jacqueline F and Humphries, Steve E (2015) 'Sixty-Five Common Genetic Variants and Prediction of Type 2 Diabetes.' Diabetes, 64 (5). pp. 1830-1840. ISSN 0012-1797

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Abstract

<jats:p>We developed a 65 type 2 diabetes (T2D) variant–weighted gene score to examine the impact on T2D risk assessment in a U.K.-based consortium of prospective studies, with subjects initially free from T2D (N = 13,294; 37.3% women; mean age 58.5 [38–99] years). We compared the performance of the gene score with the phenotypically derived Framingham Offspring Study T2D risk model and then the two in combination. Over the median 10 years of follow-up, 804 participants developed T2D. The odds ratio for T2D (top vs. bottom quintiles of gene score) was 2.70 (95% CI 2.12–3.43). With a 10% false-positive rate, the genetic score alone detected 19.9% incident cases, the Framingham risk model 30.7%, and together 37.3%. The respective area under the receiver operator characteristic curves were 0.60 (95% CI 0.58–0.62), 0.75 (95% CI 0.73 to 0.77), and 0.76 (95% CI 0.75 to 0.78). The combined risk score net reclassification improvement (NRI) was 8.1% (5.0 to 11.2; P = 3.31 × 10−7). While BMI stratification into tertiles influenced the NRI (BMI ≤24.5 kg/m2, 27.6% [95% CI 17.7–37.5], P = 4.82 × 10−8; 24.5–27.5 kg/m2, 11.6% [95% CI 5.8–17.4], P = 9.88 × 10−5; &amp;gt;27.5 kg/m2, 2.6% [95% CI −1.4 to 6.6], P = 0.20), age categories did not. The addition of the gene score to a phenotypic risk model leads to a potentially clinically important improvement in discrimination of incident T2D.</jats:p>

Item Type: Article
Uncontrolled Keywords: UCLEB Consortium; Humans; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Body Mass Index; Odds Ratio; Risk Factors; Sex Factors; Aging; Genotype; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Male
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences
Faculty of Social Sciences > Institute for Social and Economic Research
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 02 Jul 2015 13:45
Last Modified: 14 Mar 2022 23:51
URI: http://repository.essex.ac.uk/id/eprint/14211

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