Khoury M J, Wagener D K
Birth Defects and Genetic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Am J Hum Genet. 1995 Apr;56(4):835-44.
The prevention of common diseases relies on identifying risk factors and implementing intervention in high-risk groups. Nevertheless, most known risk factors have low positive predictive value (PPV) and low population-attributable fraction (PAF) for diseases (e.g., cholesterol and coronary heart disease). With advancing genetic technology, it will be possible to refine the risk-factor approach to target intervention to individuals with risk factors who also carry disease-susceptibility allele(s). We provide an epidemiological approach to assess the impact of genetic testing on the PPV and PAF associated with risk factors. Under plausible models of interaction between a risk factor and a genotype, we derive values of PPV and PAF associated with the joint effects of a risk factor and a genotype. The use of genetic testing can markedly increase the PPV of a risk factor. PPV increases with increasing genotype-risk factor interaction and increasing marginal relative risk associated with the factor, but it is inversely proportional to the prevalences of the genotype and the factor. For example, for a disease with lifetime risk of 1%, if all the risk-factor effect is confined to individuals with a susceptible genotype, a risk factor with 10% prevalence and disease relative risk of 2 in the population will have a disease PPV of 1.8%, but it will have a PPV of 91.8% among persons with a genotype of 1% prevalence. On the other hand, genetic testing and restriction of preventive measures to those susceptible may decrease the PAF of the risk factor, especially at low prevalences of the risk factor and genotype.(ABSTRACT TRUNCATED AT 250 WORDS)
常见疾病的预防依赖于识别风险因素并对高危人群实施干预。然而，大多数已知的风险因素对疾病的阳性预测值（PPV）和人群归因分数（PAF）较低（例如，胆固醇与冠心病）。随着基因技术的进步，有可能改进风险因素方法，将干预目标对准既具有风险因素又携带疾病易感等位基因的个体。我们提供一种流行病学方法来评估基因检测对与风险因素相关的PPV和PAF的影响。在风险因素与基因型之间相互作用的合理模型下，我们推导出与风险因素和基因型联合效应相关的PPV和PAF值。基因检测的使用可显著提高风险因素的PPV。PPV随着基因型 - 风险因素相互作用的增加以及与该因素相关的边际相对风险的增加而增加，但它与基因型和因素的患病率成反比。例如，对于一种终生风险为1%的疾病，如果所有风险因素效应都局限于具有易感基因型的个体，在人群中患病率为10%且疾病相对风险为2的风险因素，其疾病PPV为1.8%，但在基因型患病率为1%的人群中其PPV将为91.8%。另一方面，基因检测以及将预防措施限制于易感人群可能会降低风险因素的PAF，尤其是在风险因素和基因型患病率较低时。（摘要截短为250字）
