Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.
Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.
复制标题
评估18种常见遗传变异的综合遗传变异对2型糖尿病风险的综合影响。
作者：
Lango H;UK Type 2 Diabetes Genetics Consortium;Palmer CN;Morris AD;Zeggini E;Hattersley AT;McCarthy MI;Frayling TM;Weedon MN
目标 - 整个基因组的关联研究显着增加了与2型糖尿病牢固相关的常见遗传变异的数量。在这里更有效地针对性。
研究设计和方法 - 我们评估了2,598名对照受试者的18个独立局部核苷酸多态性（SNP）和来自糖尿病审计和研究Tayside研究的2,309例病例受试者。基于携带的风险等位基因数量并确定2型糖尿病的相对几率的个体，并通过计算接收器操作员特征曲线（AUC）下的面积。
结果 - 例如，携带更多风险等位基因的个人患有2型糖尿病的风险。风险等位基因。
结论 - 目前，2型糖尿病的常见风险变异在人群水平上没有提供强大的预测价值，风险变异的联合效应确定了人口的亚组，是否需要进一步的疾病风险。由于基因检测，高等风险等位基因可能会受益。
OBJECTIVES—Genome-wide association studies have dramatically increased the number of common genetic variants that are robustly associated with type 2 diabetes. A possible clinical use of this information is to identify individuals at high risk of developing the disease, so that preventative measures may be more effectively targeted. Here, we assess the ability of 18 confirmed type 2 diabetes variants to differentiate between type 2 diabetic case and control subjects. RESEARCH DESIGN AND METHODS—We assessed index single nucleotide polymorphisms (SNPs) for the 18 independent loci in 2,598 control subjects and 2,309 case subjects from the Genetics of Diabetes Audit and Research Tayside Study. The discriminatory ability of the combined SNP information was assessed by grouping individuals based on number of risk alleles carried and determining relative odds of type 2 diabetes and by calculating the area under the receiver-operator characteristic curve (AUC). RESULTS—Individuals carrying more risk alleles had a higher risk of type 2 diabetes. For example, 1.2% of individuals with >24 risk alleles had an odds ratio of 4.2 (95% CI 2.11–8.56) against the 1.8% with 10–12 risk alleles. The AUC (a measure of discriminative accuracy) for these variants was 0.60. The AUC for age, BMI, and sex was 0.78, and adding the genetic risk variants only marginally increased this to 0.80. CONCLUSIONS—Currently, common risk variants for type 2 diabetes do not provide strong predictive value at a population level. However, the joint effect of risk variants identified subgroups of the population at substantially different risk of disease. Further studies are needed to assess whether individuals with extreme numbers of risk alleles may benefit from genetic testing.
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影响因子：
158.5
作者：
Knowler, WC;Barrett-Connor, E;Nathan, DM
通讯作者：
Nathan, DM
DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
8.8
作者：
Janssens, A. Cecile J. W.;Moonesinghe, Ramal;Khoury, Muin J.
通讯作者：
Khoury, Muin J.