Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Nat Genet. 2019 Apr;51(4):584-591. doi: 10.1038/s41588-019-0379-x. Epub 2019 Mar 29.
Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine. However, the major ethical and scientific challenge surrounding clinical implementation of PRS is that those available today are several times more accurate in individuals of European ancestry than other ancestries. This disparity is an inescapable consequence of Eurocentric biases in genome-wide association studies, thus highlighting that-unlike clinical biomarkers and prescription drugs, which may individually work better in some populations but do not ubiquitously perform far better in European populations-clinical uses of PRS today would systematically afford greater improvement for European-descent populations. Early diversifying efforts show promise in leveling this vast imbalance, even when non-European sample sizes are considerably smaller than the largest studies to date. To realize the full and equitable potential of PRS, greater diversity must be prioritized in genetic studies, and summary statistics must be publically disseminated to ensure that health disparities are not increased for those individuals already most underserved.
多基因风险评分(PRS)有望通过精准医学改善生物医学结果。然而,PRS 临床应用所面临的主要伦理和科学挑战是,目前可用的评分在欧洲血统个体中的准确性比其他血统高出数倍。这种差异是全基因组关联研究中欧洲中心主义偏见不可避免的后果,因此,与临床生物标志物和处方药不同,后者在某些人群中可能效果更好,但在欧洲人群中并非普遍效果更好——PRS 的临床应用今天将为欧洲血统人群系统地提供更大的改善。早期的多样化努力显示出有希望缩小这一巨大差距,即使非欧洲人群的样本量明显小于迄今为止最大的研究。为了充分实现 PRS 的潜力和平等机会,遗传研究必须优先考虑多样性,并公开传播汇总统计数据,以确保已经服务不足的人群的健康差距不会进一步扩大。