Baker Emily, Escott-Price Valentina
UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff University, Cardiff, United Kingdom.
MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Front Digit Health. 2020 Aug 11;2:14. doi: 10.3389/fdgth.2020.00014. eCollection 2020.
Genome-wide association studies have identified nearly 40 genome-wide significant single nucleotide polymorphisms (SNPs) which are associated with Alzheimer's Disease (AD). Due to the polygenicity of AD, polygenic risk scores (PRS) have shown high potential for AD risk prediction. PRSs have been shown to successfully discriminate between AD cases and controls achieving a prediction accuracy of up to 84% based on area under the receiver operating curve. The prediction accuracy in AD is higher compared with other complex genetic disorders. PRS can be restricted to SNPs which reside in biologically relevant gene-sets; the predictive value of these gene-sets in the general population is not as high as genome-wide PRS, but they may play an important role to identify mechanisms of disease development and inform biological experiments. Multiple methods are available to derive PRSs, such as selecting SNPs based on statistical evidence of association with the disease or using prior evidence for SNP selection. All methods have advantages, but PRS produced using different methodologies are often not comparable, and results should be interpreted with care. Similarly, this is true when PRS is based on different background populations. With the exponential growth in development of digital electronic devices it is easy to calculate an individual's disease risk using public databases. A major limitation for the utility of PRSs is that the risk score is sample and method dependent. Therefore, replicability and interpretability of PRS is an important issue. PRS can be used to determine the probability of developing disease which incorporates information about disease risk in the general population or in a specific AD risk group. It is essential to consult with genetic counselors to ensure genetic risk is communicated appropriately.
全基因组关联研究已经确定了近40个全基因组显著的单核苷酸多态性(SNP),这些多态性与阿尔茨海默病(AD)相关。由于AD的多基因性,多基因风险评分(PRS)在AD风险预测方面显示出很高的潜力。PRS已被证明能够成功地区分AD病例和对照,基于受试者工作特征曲线下面积,预测准确率高达84%。与其他复杂的遗传疾病相比,AD的预测准确率更高。PRS可以局限于位于生物学相关基因集内的SNP;这些基因集在普通人群中的预测价值不如全基因组PRS高,但它们可能在识别疾病发展机制和为生物学实验提供信息方面发挥重要作用。有多种方法可用于推导PRS,例如根据与疾病关联的统计证据选择SNP或使用先验证据进行SNP选择。所有方法都有优点,但使用不同方法产生的PRS往往不可比,结果应谨慎解释。同样,当PRS基于不同的背景人群时也是如此。随着数字电子设备发展的指数级增长,利用公共数据库很容易计算个体的疾病风险。PRS实用性的一个主要限制是风险评分依赖于样本和方法。因此,PRS的可重复性和可解释性是一个重要问题。PRS可用于确定患疾病的概率,该概率纳入了普通人群或特定AD风险组中疾病风险的信息。咨询遗传咨询师以确保适当传达遗传风险至关重要。