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Eur J Hum Genet. 2010 Apr;18(4):485-9. doi: 10.1038/ejhg.2009.209. Epub 2009 Nov 25.
Genetic testing for susceptibility to common diseases based on a combination of genetic markers may be needed because the effect size associated with each genetic marker is small. Whether or not a genome profile based on a combination of markers could yield a useful test can be evaluated by assessing the discriminative accuracy. The authors present a simple method to calculate the clinical discriminative accuracy of a genomic profile when the relative risk and genotype frequency of each genotype are known. In addition, the clinical discriminative accuracy of a genetic test is presented for given values of the heritability and prevalence of the disease and for the population-attributable fraction of the combined genetic markers. For given values of relative risk and genotype frequency, the discriminative accuracy increases with increasing heritability but declines with increasing prevalence of the disease. For a given value of population-attributable fraction, the discriminative accuracy increases with increasing relative risks, but declines with increasing genotype frequency. On the basis of population-attributable fraction and estimates of heritability of disease, the number of risk genotypes required to have a reasonable clinical discriminative accuracy is much higher than the genome profiles available at present.
基于遗传标记组合的常见疾病易感性基因检测可能是必要的，因为与每个遗传标记相关的效应大小较小。可以通过评估判别准确性来评估基于标记组合的基因组图谱是否可以产生有用的测试。当已知每个基因型的相对风险和基因型频率时，作者提出了一种简单的方法来计算基因组图谱的临床判别准确性。此外，还针对疾病的遗传率和患病率以及组合遗传标记的人群归因分数的给定值，给出了遗传检测的临床判别准确性。对于给定的相对风险和基因型频率，判别准确性随遗传率的增加而增加，但随疾病患病率的增加而降低。对于给定的人群归因分数，判别准确性随相对风险的增加而增加，但随基因型频率的增加而降低。基于人群归因分数和疾病遗传率的估计，具有合理临床判别准确性所需的风险基因型数量远远高于目前可用的基因组图谱。
