Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
Genome Institute of Singapore, ASTAR, Singapore; Cardiovascular Research Institute, National University of Singapore, National University Health System, Singapore.
EBioMedicine. 2016 Feb 4;5:211-6. doi: 10.1016/j.ebiom.2016.01.030. eCollection 2016 Mar.
In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated to the patient's primary condition, is between 0.86% and 8.8%. However, data on prevalence and type of IFs in Asian population is lacking.
In 2 cohorts of individuals with genomic sequencing performed in Singapore (total n = 377), we extracted and annotated variants in the 56 ACMG-recommended genes and filtered these variants based on the level of pathogenicity. We then analyzed the precise distribution of IFs, class of genes, related medical conditions, and potential clinical impact.
We found a total of 41,607 variants in the 56 genes in our cohort of 377 individuals. After filtering for rare and coding variants, we identified 14 potential variants. After reviewing primary literature, only 4 out of the 14 variants were classified to be pathogenic, while an additional two variants were classified as likely pathogenic. Overall, the cumulative prevalence of IFs (pathogenic and likely pathogenic variants) in our cohort was 1.6%.
The cumulative prevalence of IFs through genomic sequencing is low and the incidentalome may not be a significant barrier to implementation of genomics for personalized medicine.
在西方队列中，偶然发现（IFs）或偶然基因组，指与患者主要病情无关的基因变异，其患病率在 0.86%至 8.8%之间。然而，亚洲人群中关于 IFs 的患病率和类型的数据尚缺乏。
在新加坡进行基因组测序的 2 个人群队列中（总 n = 377），我们提取并注释了 56 个 ACMG 推荐基因中的变异，并根据致病性水平对这些变异进行了筛选。然后，我们分析了 IFs 的精确分布、基因类别、相关医疗状况和潜在的临床影响。
我们在 377 名个体的 56 个基因中总共发现了 41607 个变异。在对稀有和编码变异进行过滤后，我们确定了 14 个潜在的变异。在查阅原始文献后，这 14 个变异中只有 4 个被归类为致病性，另外 2 个被归类为可能致病性。总体而言，我们队列中 IFs（致病性和可能致病性变异）的累积患病率为 1.6%。
通过基因组测序偶然发现的 IFs 患病率较低，偶然基因组可能不会成为个性化医疗实施基因组学的重大障碍。
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