Purpose

Discovering an incidental finding (IF) or secondary finding (SF) is a potential result of genomic testing, but few data exist describing types and frequencies of SFs likely to appear in broader clinical populations.

Methods

The Electronic Medical Records and Genomics Network Phase III (eMERGE III) developed a CLIA-compliant sequencing panel of 109 genes and 1551 variants of clinical relevance or research interest and deployed this panel at ten clinical sites. We evaluated medically actionable SFs across 67 genes and 14 single-nucleotide variants (SNVs) in a diverse cohort of 21,915 participants drawn from a variety of settings (e.g., primary care, biobanks, specialty clinics).

Results

Correcting for testing indication, we found a 3.02% overall frequency of SFs; 2.54% from 59 genes the American College of Medical Genetics and Genomics recommends for SF return, and 0.48% in other genes, primarily HFE and PALB2. SFs associated with cancer susceptibility were most frequent (1.38%), followed by cardiovascular diseases (0.87%), and lipid disorders (0.50%). After removing HFE, the frequency of SFs and proportion of pathogenic versus likely pathogenic SFs did not differ in those self-identifying as White versus others.

Conclusion

Here we present frequencies and types of medically actionable secondary findings to support informed decision making by patients, participants, and practitioners engaged in genomic medicine.

中文翻译：

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21,915 名 eMERGE 网络参与者的基因组二次发现频率。

目的

发现偶然发现 (IF) 或次要发现 (SF) 是基因组测试的潜在结果，但很少有数据描述可能出现在更广泛临床人群中的 SF 的类型和频率。

方法

电子病历和基因组学网络第三阶段 (eMERGE III) 开发了一个符合 CLIA 的测序面板，包含 109 个基因和 1551 个具有临床相关性或研究兴趣的变体，并在十个临床地点部署了该面板。我们评估了来自不同环境（例如，初级保健、生物银行、专科诊所）的 21,915 名参与者的不同队列中 67 个基因和 14 个单核苷酸变体 (SNV) 的医学上可行的 SF。

结果

校正测试指示后，我们发现 SF 的总频率为 3.02%；2.54% 来自美国医学遗传学和基因组学学院推荐用于 SF 返回的 59 个基因，0.48% 来自其他基因，主要是HFE和PALB2。与癌症易感性相关的 SF 最常见 (1.38%)，其次是心血管疾病 (0.87%) 和血脂异常 (0.50%)。去除HFE后，SF 的频率和致病性 SF 与可能致病性 SF 的比例在那些自我识别为白人的人与其他人中没有差异。

结论

在这里，我们展示了医学上可操作的次要发现的频率和类型，以支持患者、参与者和从事基因组医学的从业者做出明智的决策。