South African National Bioinformatics Institute (SANBI), University of Western Cape, Cape Town, South Africa.
Global Genomic Medicine Collaborative, Durham, NC, USA.
Hum Genet. 2022 Nov;141(11):1697-1704. doi: 10.1007/s00439-022-02452-x. Epub 2022 Apr 30.
Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translational research is still needed before they should enter mainstream clinical practice.
基因组医学旨在利用个体的基因组数据来改善健康状况,为医疗提供信息。虽然基因组医学在许多单基因、孟德尔疾病中的临床应用已经得到充分证明,但在多基因性状(如冠状动脉疾病或乳腺癌)中的临床应用则不太明显。多基因风险评分(PRS)是个体基因型的子集,旨在捕捉常见性状的遗传度,从而允许对人群中该性状的风险进行分层。我们使用严格的纳入和排除标准,系统地在 PubMed 数据库中检索了多基因风险评分具有明确临床实用性的证据。虽然我们确定了一些研究表明,在基于 PRS 的医疗干预可能有益于患者预后的情况下,临床有效性,但我们没有发现一项研究明确证明了这种益处,即临床实用性。我们的结论是,虽然 PRS 的常规使用前景广阔,但在它们进入主流临床实践之前,仍需要进行转化研究。
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