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Sixty-five common genetic variants and prediction of type 2 diabetes

Talmud, PJ and Cooper, JA and Morris, RW and Dudbridge, F and Shah, T and Engmann, J and Dale, C and White, J and Mclachlan, S and Zabaneh, D and Wong, A and Ong, KK and Gaunt, T and Holmes, MV and Lawlor, DA and Richards, M and Hardy, R and Kuh, D and Wareham, N and Langenberg, C and Ben-Shlomo, Y and Wannamethee, SG and Strachan, MWJ and Kumari, M and Whittaker, JC and Drenos, F and Kivimaki, M and Hingorani, AD and Price, JF and Humphries, SE (2015) 'Sixty-five common genetic variants and prediction of type 2 diabetes.' Diabetes, 64 (5). 1830 - 1840. ISSN 0012-1797

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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 followup, 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 3 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 3 10-8; 24.5-27.5 kg/m2, 11.6% [95% CI 5.8-17.4], P = 9.88 3 10-5; >27.5 kg/m2, 2.6% [95% CI 21.4 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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 02 Jul 2015 13:45
Last Modified: 21 Jun 2021 11:15

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