Sudden cardiac death (SCD) is one of the leading causes of mortality in the U.S. military and competitive athletes. In this study, we simulate how genetic screening may be implemented in the military to prevent an SCD endpoint resulting from hypertrophic cardiomyopathy (HCM). We created a logistic regression model to predict variant pathogenicity in the most common HCM associated genes MYH7 and MYBPC3. Model predictions were used in conjunction with the gnomAD database to identify frequencies of pathogenic variants. Extrapolating these variants to a military population, lives saved and cost benefit analyses were conducted for screening for HCM related to pathogenic variants in MYH7 and MYBPC3. Genetic screening for HCM followed by echocardiography in individuals with pathogenic variants is predicted to save an average of 2.9 lives per accession cohort, based on historical cohort sizes, and result in a break-even cost of ~$7 per test. The false positives, defined as disqualified individuals for military service who do not have HCM, are predicted to be 0 individuals per accession cohort. This study suggests that the main barriers for the implementation of genetic screening for the U.S. military are the low detection rate and variant interpretation.

中文翻译：

---

大型无症状军事人群肥厚型心肌病的基因筛查。

心脏猝死（SCD）是美国军事和竞技运动员死亡的主要原因之一。在这项研究中，我们模拟了如何在军队中进行基因筛查，以预防由肥厚型心肌病（HCM）导致的SCD终点。我们创建了一个逻辑回归模型来预测最常见的HCM相关基因MYH7和MYBPC3的变异致病性。模型预测与gnomAD数据库一起使用，以识别病原体变异的频率。将这些变异体推断给军人，进行了挽救的生命和成本效益分析，以筛选与MYH7和MYBPC3中的致病变异体相关的HCM。对具有致病变异的个体进行HCM的基因筛查，然后进行超声心动图检查，预计平均可节省2。根据历史队列人数，每个入组队列9条生命，每项测试的收支平衡成本约为7美元。误报定义为没有HCM的不符合兵役条件的个人，每个入组队列预测为0个人。这项研究表明，对美军实施基因筛选的主要障碍是检测率低和变异解释。