Jansen Philip R, Broeders Mireille J M, Cornel Martina C, Meijers-Heijboer Hanne
Amsterdam UMC, afd. Klinische Genetica, Amsterdam.
Contact: P.R. Jansen (
Ned Tijdschr Geneeskd. 2019 Sep 24;163:D3870.
Since the first map of the human genome was published in 2001 our knowledge about our genetic code has increased exponentially. In addition to high-risk genes for monogenic diseases, such as Huntington's disease and cystic fibrosis, for a number of common diseases, such as breast cancer and cardiovascular disease, many genetic variants that each have a slight increased-risk effect, have been identified via genome-wide association studies (GWAS). A polygenic risk score (PRS) can be calculated on the basis of these single-nucleotide polymorphisms (SNPs), by which an increasingly accurate prediction can be made of an individual's risk for diseases. The results of epidemiological studies in which a PRS is used to predict an individual's total genetic risk for particular diseases are promising. In the future, the PRS could be a valuable addition to traditional monogenic tests. It is, however, important that the predictive value of a genetic risk profile increases further and that it becomes more clear how a clinician must interpret this type of genetic profile - in combination with traditional risk factors.
自2001年人类基因组首张图谱公布以来，我们对遗传密码的了解呈指数级增长。除了亨廷顿舞蹈症和囊性纤维化等单基因疾病的高风险基因外，通过全基因组关联研究（GWAS），还发现了许多对乳腺癌和心血管疾病等多种常见疾病有轻微风险增加效应的基因变异。基于这些单核苷酸多态性（SNP）可以计算出多基因风险评分（PRS），据此能够对个体患疾病的风险做出越来越准确的预测。使用PRS预测个体患特定疾病的总体遗传风险的流行病学研究结果很有前景。未来，PRS可能会成为传统单基因检测的一项有价值的补充。然而，重要的是遗传风险概况的预测价值要进一步提高，并且临床医生如何结合传统风险因素来解读这类遗传概况要更加明确。
