Development of a clinical polygenic risk score assay and reporting workflow.
Development of a clinical polygenic risk score assay and reporting workflow.
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DOI：
10.1038/s41591-022-01767-6
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发表时间：
2022-05
期刊：
影响因子：
82.9
通讯作者：
Lebo, Matthew S.
中科院分区：
文献类型：
--
作者：
Hao, Limin;Kraft, Peter;Berriz, Gabriel F.;Hynes, Elizabeth D.;Koch, Christopher;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.
多基因风险评分（PRS）的实施可以改善疾病预防和管理，但也带来了一些挑战：构建临床有效的检测方法，对个体患者的解释，以及开发临床工作流程和资源以支持其在患者护理中的使用。对于正在进行的退伍军人事务部基因组医学（热那亚）研究，我们开发了一种基于临床基因型阵列的检测方法，用于6种已发表的PRS。我们使用了来自36，423名Mass General Brigham Biobank参与者的数据，并对人群结构进行了调整，以复制已知的PRS-疾病相关性，并公布了疾病比值比（OR）为2的PRS阈值（范围从2型糖尿病的1.75（95%CI：1.57-1.95）到乳腺癌的2.38（95%CI：2.07-2.73））。在确认管道用作个体患者临床检测的高性能和稳健性后，我们分析了来自热那亚研究的前227个前瞻性样本，发现对应于已发表OR > 2的PRS频率范围从结直肠癌的13/227（5.7%）到前列腺癌的23/150（15.3%）。除了PRS实验室报告外，我们还开发了面向医生和患者的信息材料，以支持有关PRS结果的决策。我们的工作说明了临床PRS测定的多种条件和技术，报告和临床工作流程的挑战，在临床上实施PRS信息的普遍发展。前瞻性热那亚研究的第一份报告提供了在临床环境中开发多基因风险评分测定的初步见解，并讨论了生成、解释和报告结果的挑战。
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. The first report from the prospective GenoVA Study provides preliminary insights into the development of a polygenic risk score assay in a clinical setting and discusses the challenges of generating, interpreting and reporting results.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
12.3
作者：
Chen SF;Dias R;Evans D;Salfati EL;Liu S;Wineinger NE;Torkamani A
通讯作者：
Torkamani A
DOI：
10.1056/nejmsr1809937
发表时间：
2019-08-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
All of Us Research Program Investigators;Denny JC;Rutter JL;Goldstein DB;Philippakis A;Smoller JW;Jenkins G;Dishman E
通讯作者：
Dishman E
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ