Genomic and Environmental Determinants of Infant Deaths in San Diego County in 2015-2022

项目摘要 全球每年都会对婴儿死亡率进行跟踪。对婴儿死亡原因的了解塑造了公共卫生 在监测、干预和医学研究方面的投资中，政策和优先考虑疾病。结果, 在过去的50年里，导致婴儿死亡的多种原因的比率显著下降。建议数 研究团队开创了一种新的方法来降低与14,000名婴儿相关的发病率和死亡率 遗传病，称为基因组医学：在基因组医学中，基因组测序可以提供遗传病诊断 只有19个小时。重症婴儿的早期遗传病诊断允许经验性的初步治疗 取而代之的是针对该疾病的特定循证治疗。在对681名重病儿童的9项研究中， 基因组测序诊断为31%，21%的人在治疗中有相应的变化，13%的人在治疗中有变化 结果。因此，基因组药物在重病婴儿中得到了广泛的接受。然而，对于 基因组医学最大限度地降低婴儿发病率和死亡率，并预期基因的价值 在诊断中，关键是要在其他因素的背景下确定导致婴儿死亡的主要遗传原因 环境因素。我们建议使用基因组测序和半自动解释来识别 2015至2022年间，与圣地亚哥县1000名婴儿死亡有关的遗传病以及 评估环境对这些婴儿死亡的潜在贡献。我们将潜在地确定 通过确定与特定遗传病相关的死亡来预防婴儿死亡 众所周知，有针对性的干预可以降低死亡率。这一新知识将使政策制定者 研究人员和临床医生将这些疾病列为优先事项，投资于新的挽救生命的干预措施和 治疗。

Project Summary Infant mortality is tracked annually worldwide. Knowledge of causes of infant mortality shapes public health policy and prioritizes diseases for investments in surveillance, intervention and medical research. As a result, rates of many causes of infant mortality have declined significantly over the past 50 years. The proposed research team has pioneered a new way to decrease infant morbidity and mortality associated with 14,000 genetic diseases, called genomic medicine: In it, genome sequencing can provide a genetic disease diagnosis in as little as 19 hours. Early genetic disease diagnosis in seriously ill infants allows empiric initial treatment to be replaced with specific evidence-based treatment for that condition. In 9 studies of 681 seriously ill children, genomic sequencing diagnosed 31%, 21% had consequent changes in treatment, and 13% had changes in outcome. As a result, genomic medicine is gaining broad acceptance in seriously ill infants. However, for genomic medicine to decrease infant morbidity and mortality maximally and to anticipate the value of genetic diagnoses, it is critical to determine the leading genetic causes of infant mortality in the context of other environmental factors. We propose to use genome sequencing and semi-automated interpretation to identify genetic diseases associated with 1,000 infant deaths in San Diego County between 2015 and 2022 and to evaluate potential environmental contributions to those same infant deaths. We will identify potentially preventable infant deaths by determining those deaths associated with specific genetic diseases for which targeted interventions are known to reduce mortality. This new knowledge will enable policymakers, researchers, and clinicians to prioritize those diseases for investments in new, life-saving interventions and treatments.