近日，美国哈佛医学院Jason L. Vassy团队完成临床多基因风险评分检测和报告工作流程的开发。相关论文于2022年4月18日在线发表在《自然—医学》杂志上。

Author: Hao, Limin, Kraft, Peter, Berriz, Gabriel F., Hynes, Elizabeth D., Koch, Christopher, Korategere V Kumar, Prathik, Parpattedar, Shruti S., Steeves, Marcie, Yu, Wanfeng, Antwi, Ashley A., Brunette, Charles A., Danowski, Morgan, Gala, Manish K., Green, Robert C., Jones, Natalie E., Lewis, Anna C. F., Lubitz, Steven A., Natarajan, Pradeep, Vassy, Jason L., Lebo, Matthew S.

Issue&Volume: 2022-04-18

Abstract: Implementation of polygenic risk scores (PRS) may improve disease prevention and management but poses several challenges: the construction of clinically valid assays, interpretation for individual patients, and the development of clinical workflows and resources to support their use in patient care. For the ongoing Veterans Affairs Genomic Medicine at Veterans Affairs (GenoVA) Study we developed a clinical genotype array-based assay for six published PRS. We used data from 36,423 Mass General Brigham Biobank participants and adjustment for population structure to replicate known PRS–disease associations and published PRS thresholds for a disease odds ratio (OR) of 2 (ranging from 1.75 (95% CI: 1.57–1.95) for type 2 diabetes to 2.38 (95% CI: 2.07–2.73) for breast cancer). After confirming the high performance and robustness of the pipeline for use as a clinical assay for individual patients, we analyzed the first 227 prospective samples from the GenoVA Study and found that the frequency of PRS corresponding to published OR>2 ranged from 13/227 (5.7%) for colorectal cancer to 23/150 (15.3%) for prostate cancer. In addition to the PRS laboratory report, we developed physician- and patient-oriented informational materials to support decision-making about PRS results. Our work illustrates the generalizable development of a clinical PRS assay for multiple conditions and the technical, reporting and clinical workflow challenges for implementing PRS information in the clinic.

DOI: 10.1038/s41591-022-01767-6

Source: https://www.nature.com/articles/s41591-022-01767-6