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

Diabetes (New York, N.Y.), 2015-05, Vol.64 (5), p.1830-1840 [Peer Reviewed Journal]

2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. ;Copyright American Diabetes Association May 2015 ;2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. 2015 ;ISSN: 0012-1797 ;EISSN: 1939-327X ;DOI: 10.2337/db14-1504 ;PMID: 25475436 ;CODEN: DIAEAZ

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Title:
Sixty-five common genetic variants and prediction of type 2 diabetes
Author: Talmud, Philippa J ; Cooper, Jackie A ; Morris, Richard W ; Dudbridge, Frank ; Shah, Tina ; Engmann, Jorgen ; Dale, Caroline ; White, Jon ; McLachlan, Stela ; Zabaneh, Delilah ; Wong, Andrew ; Ong, Ken K ; Gaunt, Tom ; Holmes, Michael V ; Lawlor, Debbie A ; Richards, Marcus ; Hardy, Rebecca ; Kuh, Diana ; Wareham, Nicholas ; Langenberg, Claudia ; Ben-Shlomo, Yoav ; Wannamethee, S Goya ; Strachan, Mark W J ; Kumari, Meena ; Whittaker, John C ; Drenos, Fotios ; Kivimaki, Mika ; Hingorani, Aroon D ; Price, Jacqueline F ; Humphries, Steve E
Subjects: Adult ; Aged ; Aged, 80 and over ; Aging ; Body Mass Index ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Female ; Genetic Predisposition to Disease ; Genetics ; Genetics/Genomes/Proteomics/Metabolomics ; Genotype ; Genotype & phenotype ; Humans ; Male ; Middle Aged ; Odds Ratio ; Predictions ; Risk assessment ; Risk Factors ; Sex Factors
Is Part Of: Diabetes (New York, N.Y.), 2015-05, Vol.64 (5), p.1830-1840
Description: 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/m(2), 27.6% [95% CI 17.7-37.5], P = 4.82 × 10(-8); 24.5-27.5 kg/m(2), 11.6% [95% CI 5.8-17.4], P = 9.88 × 10(-5); >27.5 kg/m(2), 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.
Publisher: United States: American Diabetes Association
Language: English
Identifier: ISSN: 0012-1797
EISSN: 1939-327X
DOI: 10.2337/db14-1504
PMID: 25475436
CODEN: DIAEAZ
Source: MEDLINE
PubMed Central
Alma/SFX Local Collection

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

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