Genotype score in addition to common risk factors for prediction of type 2 diabetes.
N Engl J Med
; 359(21): 2208-19, 2008 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-19020323
ABSTRACT
BACKGROUND:
Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested the hypothesis that knowledge of these loci allows better prediction of risk than knowledge of common phenotypic risk factors alone.METHODS:
We genotyped single-nucleotide polymorphisms (SNPs) at 18 loci associated with diabetes in 2377 participants of the Framingham Offspring Study. We created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors.RESULTS:
There were 255 new cases of diabetes during 28 years of follow-up. The mean (+/-SD) genotype score was 17.7+/-2.7 among subjects in whom diabetes developed and 17.1+/-2.6 among those in whom diabetes did not develop (P<0.001). The sex-adjusted odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P=0.01). In a model adjusted for sex and self-reported family history of diabetes, the C statistic was 0.595 without the genotype score and 0.615 with the score (P=0.11). In a model adjusted for age, sex, family history, body-mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score (P=0.49). The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects.CONCLUSIONS:
A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Diabetes Mellitus Tipo 2
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Genótipo
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos