A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.
A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.
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DOI：
10.1038/gim.2015.104
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发表时间：
2016-05
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通讯作者：
Evans JP
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作者：
Berg JS;Foreman AK;O'Daniel JM;Booker JK;Boshe L;Carey T;Crooks KR;Jensen BC;Juengst ET;Lee K;Nelson DK;Powell BC;Powell CM;Roche MI;Skrzynia C;Strande NT;Weck KE;Wilhelmsen KC;Evans JP
随着基因组规模测序越来越多地应用于临床场景，各种各样的基因组发现将被发现为次要或偶然发现，并且关于如何处理它们存在争议。这些发现的临床可操作性各不相同，需要标准化的框架来对其分析进行先验决策。Genet Med 18 5，467-475.我们建立了一个半定量指标来评估可行动性的五个要素：疾病结局的严重程度和可能性、干预的有效性和负担以及知识基础，总分为0至15分。Genet Med 18 5，467-475.半定量指标被应用于一系列假定的可操作条件，美国医学遗传学和基因组学学院（ACMG）推荐的基因列表，当发现有害变异作为次要/偶然发现时，以及1,000个基因的随机样本。来自推定的可采取行动的状况列表（中值= 12）和ACMG列表（中值= 11）的评分均与随机选择的基因（中值= 7）具有统计学差异（P < 0.0001，双尾Mann-Whitney检验）。Genet Med 18 5，467-475.得分为11或更高的基因-疾病对代表可采取行动的前五分之一。半定量指标有效地评估临床可操作性，提高透明度，并可能促进不同群体和不同背景下的临床可操作性评估。Genet Med 18 5，467-475.
As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis. Genet Med 18 5, 467–475. We established a semiquantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0 to 15. Genet Med 18 5, 467–475. The semiquantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics and Genomics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1,000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (P < 0.0001, two-tailed Mann-Whitney test). Genet Med 18 5, 467–475. Gene–disease pairs having a score of 11 or higher represent the top quintile of actionability. The semiquantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts. Genet Med 18 5, 467–475.