Genotype score in addition to common risk factors for prediction of type 2 diabetes.
Genotype score in addition to common risk factors for prediction of type 2 diabetes.
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DOI：
10.1056/nejmoa0804742
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发表时间：
2008-11-20
期刊：
影响因子：
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通讯作者：
Cupples LA
中科院分区：
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作者：
Meigs JB;Shrader P;Sullivan LM;McAteer JB;Fox CS;Dupuis J;Manning AK;Florez JC;Wilson PW;D'Agostino RB Sr;Cupples LA
多个遗传位点已令人信服地与2型糖尿病的风险相关。我们检验了这样一个假设，即对这些基因座的了解比仅对常见表型危险因素的了解更能预测风险。我们对2377名参与Frachial Offspring研究的糖尿病相关的18个位点的单核苷酸多态性（SNP）进行了基因分型。我们从风险等位基因的数量中创建了一个基因型得分，并使用逻辑回归来生成C统计，表明基因型得分在单独使用和与临床风险因素一起使用时可以区分糖尿病风险的程度。在28年的随访中，有255例新发糖尿病病例。发生糖尿病的受试者的平均（±SD）基因型得分为17.7±2.7，未发生糖尿病的受试者的平均（± SD）基因型得分为17.1±2.6（P<0.001）。糖尿病的性别调整优势比为每个危险等位基因1.12（95%置信区间，1.07至1.17）。C统计量为0.581，无基因型得分（P=0.01）和0.534。在调整性别和自我报告的糖尿病家族史的模型中，C统计量为0.595（无基因型评分）和0.615（有评分）（P=0.11）。在校正了年龄、性别、家族史、体重指数、空腹血糖水平、收缩压、高密度脂蛋白胆固醇水平和甘油三酯水平的模型中，C统计量为0.900（不含基因型评分）和0.901（含基因型评分）（P=0.49）。基因型得分导致最多4%的受试者的适当风险重新分类。基于18个风险等位基因的基因型评分预测社区中糖尿病的新发病例，但仅比仅了解常见风险因素的预测略好。
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. 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. 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. 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.