Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?
Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?
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DOI：
10.1038/gim.2013.9
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发表时间：
2013-08-01
影响因子：
8.8
通讯作者：
Douglas, Michael P.
中科院分区：
文献类型：
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作者：
Calonge, Ned;Berg, Jonathan S.;Douglas, Michael P.
基因组在实践和预防中的应用评估（EGAPP）工作组（EWG）发现，在北欧血统人群的研究基础上，没有足够的证据推荐对28种变异（见表1）进行预测变异检测，以评估普通人群中2型糖尿病的风险。EWG发现，单独使用或组合使用这些测试中的任何一种所带来的净健康效益接近于零。EWG不鼓励临床使用，除非有进一步的证据支持改善临床结果。EWG发现没有足够的证据推荐检测TCF7L2基因来评估高危人群患2型糖尿病的风险。EWG发现，使用这种测试的净健康效益接近于零。EWG不鼓励临床使用，除非有进一步的证据支持改善临床结果。根据这两种情况的现有证据，净健康效益的总体确定性被认为是“低的”。“理由：有人建议，在普通人群或2型糖尿病高危人群中进行基因组分析可能会导致管理上的改变（例如，更早开始或更高的医疗干预率，或有针对性的行为改变建议），从而改善2型糖尿病的结局或预防2型糖尿病。EWG没有发现支持这种可能性的直接证据；因此，本综述寻求间接证据，旨在记录基因组谱在多大程度上改变2型糖尿病风险评估，单独或与传统风险因素结合，以及风险分类在多大程度上改善健康结果。分析效度：现有基因组分析测试的分析相关证据被认为是不充分的。然而，基于已经使用或可能使用的现有技术，单个基因变异检测的分析敏感性和特异性可能至少令人满意。临床效度：在普通人群中评估了28个候选标记物。其中24项（86%）临床有效性证据不足，4项（14%）临床有效性证据充足。不充分的评分是基于有限的证据、较差的复制、可能存在的偏倚或这些因素的组合。2型糖尿病基因组图谱提供了55%-57%的受体操作者特征曲线下的区域，分别有4、8和28个基因。只有TCF7L2与2型糖尿病相关，优势比为1.39（95%可信区间：1.33-1.46）。TCF7L2在高危人群中进行评估，与进展为2型糖尿病相关的总体优势比为1.66（95%可信区间：1.22-2.27）。临床应用：目前还没有研究提供直接的证据来证明基因分析对2型糖尿病单独或在普通人群中加入传统危险因素的利弊平衡。根据两项已确定的研究，高危人群和TCF7L2的证据不足。这些研究发现，在传统的风险因素（饮食、体重指数和葡萄糖耐量）之外增加基因组标记几乎没有任何额外的好处。背景问题：预防2型糖尿病是公共卫生的优先事项。与基因组分析相关的结果的改善可能会产生重要影响。传统的危险因素（如体重指数、体重、脂肪量和运动）在临床筛查和风险评估策略中具有优势，因为它们测量了治疗的实际目标（如空腹血糖和医疗干预）。为了有效地预测疾病风险，基因组检测应该提高这些传统风险因素的预测价值。一些对临床应用很重要的问题仍然未知，例如改变干预措施的风险水平，长期疾病结局是否会改善，接受检测的个体如何理解/响应检测结果并与卫生保健系统互动，以及检测是否会激发行为改变或放大潜在危害。
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) found insufficient evidence to recommend testing for predictive variants in 28 variants (listed in Table 1) to assess risk for type 2 diabetes in the general population, on the basis of studies in populations of northern European descent. The EWG found that the magnitude of net health benefit from the use of any of these tests alone or in combination is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.The EWG found insufficient evidence to recommend testing for the TCF7L2 gene to assess risk for type 2 diabetes in high-risk individuals. The EWG found that the magnitude of net health benefit from the use of this test is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.On the basis of the available evidence for both the scenarios, the overall certainty of net health benefit is deemed "low."Rationale: It has been suggested that genomic profiling in the general population or in high-risk populations for type 2 diabetes might lead to management changes (e.g., earlier initiation or higher rates of medical interventions, or targeted recommendations for behavioral change) that improve type 2 diabetes outcomes or prevent type 2 diabetes. The EWG found no direct evidence to support this possibility; therefore, this review sought indirect evidence aimed at documenting the extent to which genomic profiling alters type 2 diabetes risk estimation, alone and in combination with traditional risk factors, and the extent to which risk classification improves health outcomes.Analytic validity: Assay-related evidence on available genomic profiling tests was deemed inadequate. However, on the basis of existing technologies that have been or may be used, the analytic sensitivity and specificity of tests for individual gene variants might be at least satisfactory.Clinical validity: Twenty-eight candidate markers were evaluated in the general population. Evidence on clinical validity was rated inadequate for 24 of these associations (86%) and adequate for 4 (14%). Inadequate grades were based on limited evidence, poor replication, existence of possible biases, or combinations of these factors. Type 2 diabetes genomic profiling provided areas under the receiver operator characteristics curve of 55%-57%, with 4, 8, and 28 genes. Only TCF7L2 had convincing evidence of an association with type 2 diabetes with an odds ratio of 1.39 (95% confidence interval: 1.33-1.46). TCF7L2 was evaluated for high-risk populations, and the overall odds ratio was 1.66 (95% confidence interval: 1.22-2.27) for association with progression to type 2 diabetes.Clinical utility: No studies were available to provide direct evidence on the balance of benefits and harms for genetic profiling for type 2 diabetes alone or in addition to traditional risk factors in the general population.Evidence for high-risk populations and TCF7L2 was inadequate on the basis of two identified studies. These studies found close to zero additional benefit with the addition of genomic markers to traditional risk factors (diet, body mass index, and glucose tolerance).Contextual issues: Prevention of type 2 diabetes is a public health priority. Improvements in the outcomes associated with genomic profiling could have important impacts. Traditional risk factors (e.g., body mass index, weight, fat mass, and exercise) have an advantage in clinical screening and risk assessment strategies because they measure the actual targets for therapy (e.g., fasting plasma glucose and medical interventions). To be useful in predicting disease risk, genomic testing should improve the predictive value of these traditional risk factors. Some issues important for clinical utility remain unknown, such as the level of risk that changes intervention, whether long-term disease outcomes will improve, how individuals being tested will understand/respond to test results and interact with the health-care system, and whether testing will motivate behavior change or amplify potential harms.