Center for Biomedical Ethics and Society, Vanderbilt University, Nashville, Tennessee, USA.
Genet Med. 2013 May;15(5):325-31. doi: 10.1038/gim.2012.147. Epub 2012 Nov 29.
Greater clinical validity and economic feasibility are driving the more widespread use of multiplex genetic technologies in routine clinical care, especially for applications in pharmacogenomics. Empirical data on the numbers and types of incidental findings generated through such testing are needed to develop policies and practices related to their clinical use. Of particular importance are disparities in findings relevant to different ancestry groups.
The Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment Resource, or PREDICT, is an institutional program to implement prospective clinical genotyping of 34 pharmacogenomic-related genes to guide drug selection and dosing. We curated 5,566 journal articles to quantify and characterize the incidental, non-pharmacogenomic genotype-phenotype associations that could be generated through this clinical genotyping project.
We identified 372 putative incidental genotype-phenotype associations that might be revealed in patients undergoing clinical genotyping for pharmacogenomic purposes. Of these, 287 associations were supported by at least one study demonstrating an odds ratio ≥2.0 or ≤0.5. Numbers of potentially relevant findings varied widely by ancestry group.
Rigorous clinical policies for the clinical management of incidental findings are needed because the sheer number of significant findings could prove overwhelming to health-care institutions, providers, and patients.
为了在常规临床护理中更广泛地应用多重基因技术，特别是在药物基因组学方面，需要更高的临床有效性和经济可行性。需要有关于通过此类测试产生的偶然发现的数量和类型的经验数据，以便制定与临床应用相关的政策和实践。特别重要的是不同种族群体相关发现的差异。
药物基因组学资源增强护理和治疗决策资源（Pharmacogenomic Resource for enhanced Decisions in Care and Treatment Resource，或 PREDICT）是一个机构计划，旨在对 34 个与药物基因组学相关的基因进行前瞻性临床基因分型，以指导药物选择和剂量。我们整理了 5566 篇期刊文章，以量化和描述通过这一临床基因分型项目可能产生的偶然的、非药物基因组学的基因型-表型关联。
我们确定了 372 种可能在接受药物基因组学目的的临床基因分型的患者中出现的潜在偶然基因型-表型关联。其中，有 287 种关联至少有一项研究表明比值比≥2.0 或≤0.5。潜在相关发现的数量因种族群体而异。
需要严格的临床政策来管理偶然发现，因为大量的重要发现可能会使医疗机构、提供者和患者不堪重负。
