Using Integrative Omics as Biomarkers and Diagnostic Tools for SIDS

项目摘要 婴儿猝死综合症（SIDS）是第二大死亡原因（仅次于先天性和 遗传异常），在新生儿后期（婴儿1个月至1岁），尽管下降， 在“回到睡眠”（现在称为“安全睡眠”）降低风险运动后，发病率超过50%。在 2017年，美国有1400名婴儿死于SIDS。广泛的研究已经确定了一些流行病学风险， 小岛屿发展中国家的因素，最近的研究已经开始提供证据，遗传因素的潜在作用， 在疾病的病理生理学中的易感性。在美国，非洲裔美国人和美国人 特别是印第安人/阿拉斯加原住民婴儿患SIDS的风险更高。技术的进步现在允许 对疾病基因贡献者的更详尽的询问。本提案的目的是 综合评估SIDS的遗传和表观遗传决定因素，并确定基因表达、DNA 甲基化和代谢组学特征可能作为婴儿死亡风险更高的新生物标志物 从SIDS。我们将使用来自芝加哥婴儿死亡率研究（CIMS）的肝脏、心脏和血液标本， 美国已知最大的SUID死亡的心脏组织和心脏和血液标本的收集 NIH NeuroBioBank（NBB）研究SIDS的遗传、表观遗传和转录组学影响。 我们将采用组学方法，包括下一代测序（外显子组加RNA），全基因组测序， 表观遗传学和代谢组学分析，以鉴定预测SIDS的新生物标志物。这些发现 可能导致诊断测试和早期发现高危婴儿，从而采取预防措施， 消灭SIDS这项研究也将是第一个成功地使用综合组学方法来解决 遗传学、表观遗传学和代谢组学对SIDS的贡献。

Project Summary Sudden Infant Death Syndrome (SIDS) is the second leading cause of death (closely behind congenital and genetic abnormalities), in the postneonatal period (infants 1 month to 1 year of age), despite declines in incidence of over 50% following the Back to Sleep (now called the Safe to Sleep) risk reduction campaign. In 2017, 1400 infants in the US died of SIDS. Extensive research has identified a number of epidemiological risk factors for SIDS, and more recent research has begun to provide evidence of a potential role for genetic susceptibility in the pathophysiology of the disorder. In the United States, African American and American Indian/Alaska Native babies, in particular are at higher risk for SIDS. Advances in technology now allow for more exhaustive interrogations of genomic contributors to disease. The goal of this proposal is to comprehensively evaluate genetic and epigenetic determinates of SIDS and identify gene expression, DNA methylation and metabolomics profiles that might serve as novel biomarkers in infants at greater risk of death from SIDS. We will utilize liver, heart and blood specimens from the Chicago Infant Mortality Study (CIMS), the largest known collection of cardiac tissue from SUID deaths in the US and heart and blood specimens from the NIH NeuroBioBank (NBB) to investigate genetic, epigenetic, and transcriptomic influences of SIDS. We will employ an omics approach encompassing next generation sequencing (exome plus RNA), genome wide epigenetics, and metabolomics profiling to identify novel biomarkers that are predictive of SIDS. These findings could lead to diagnostic tests and early detection of high risk infants, resulting in preventative measures to eliminate SIDS. This study will also be the first to successfully use an integrative –Omics approach to address genetic, epigenetic, and metabolomics contributors for SIDS.