Random Field Modelling of genetic and epigenetic association underlying congenital heart defects in the presence of disease heterogeneity

项目摘要/摘要 这项建议是为了延长NHLBI K01奖的期限，该奖项的标题是：基因的随机场建模 以及在存在疾病异质性的情况下先天性心脏病的表观遗传学关联“。李明博士 是这项研究的首席研究员，并且是本K01奖的最后一年(2018年1月1日-2021年12月31日)。 在过去的一年里，李博士的研究团队经历了大量的研究中断和额外的 新冠肺炎疫情引发的行政责任。这一延期预计将为李博士提供 需要时间完成正在进行的K01项目，并成功过渡到未来的R01研究。 李博士的职业目标是成为一名独立的统计遗传学家和遗传流行病学家 心血管疾病，特别是先天性心脏病。在过去的三年里，李博士一直在 开发创新的生物统计学方法来检测与风险相关的遗传和表观遗传因素 先心病的风险。建议的方法正在应用于国家出生缺陷预防研究的样本 (NBDPS)，这是有史以来进行的最大的基于人口的多地点出生缺陷研究。到目前为止，相当可观 在同行评议期刊上发表了一些重要结论，取得了进展。其他发现 在主要会议上也作了介绍，并提交出版，但也在很大程度上遇到了延误 由于新冠肺炎的中断。这些结果提供了对潜在的病理生理学和 导致CHDS的病因过程，也将作为李博士提出更多 R01研究。未来的R01研究将主要集中在两个方面：1)应用新开发的 对其他现有NHLBI数据源的生物统计方法，如儿科心脏基因组学联盟 (2)进一步发展创新的生物统计学 基于遗传、表观遗传、转录和基因的疾病预测和精确干预方法 母亲的生活方式简介。这项研究的继续将整合NIH各机构的数据源 (即NICHD和NHLBI)，也可能为翻译研究提供方向，从而导致更精确的 孕前咨询和干预。这样的研究方向也与NHLBI的 如多个特殊利益通知中所述的重点研究领域(例如NOT-HL-20-815)。

Project Summary/Abstract This proposal is submitted for an extension of the NHLBI K01 award, entitled “Random field modeling of genetic and epigenetic associations for congenital heart defects in the presence of disease heterogeneity”. Dr. Ming Li is the principal investigator of this study, and is within the final year of this K01 award (01/01/2018 – 12/31/2021). In the past year, Dr. Li’s research team has experienced substantial research interruptions and additional administrative responsibilities due to the COVID-19 pandemic. This extension is expected to provide Dr. Li the necessary time to complete the ongoing K01 projects and to make successfully transition to future R01 studies. Dr. Li’s career goal is to become an independent statistical geneticist and genetic epidemiologist in cardiovascular diseases, particularly in congenital heart defects (CHDs). In the past three years, Dr. Li has been developing innovative biostatistical methods for detecting genetic and epigenetic factors associated with the risk of CHDs. The proposed methods are being applied to samples from the National Birth Defect Prevention Study (NBDPS), the largest multi-site population-based study of birth defects ever conducted. So far, substantial progresses have been made with a number of key findings published in peer-review journals. Additional findings were also presented at the major conferences and submitted for publications, but also experienced delays largely due to COVID-19 interruptions. These results have provided insights into the underlying pathophysiological and etiological processes that result in CHDs, and will also serve as a foundation for Dr. Li to make propose additional R01 studies. The future R01 studies will mainly be focused on two aspects: 1) to apply the newly developed biostatical methods to other existing NHLBI data sources, such as the Pediatric Cardiac Genomics Consortium (PCGC) and Trans-Omics for Precision Medicine (TOPMed); and 2) to further develop innovative biostatistical methods for disease prediction and precision intervention based on the genetic, epigenetic, transcriptional and maternal lifestyle profiles. The continuation of this research will integrate data sources across NIH institutions (i.e. NICHD and NHLBI), and also may provide a direction for translational research leading to more precise preconceptional counseling and interventions. Such research directions are also consistent with NHLBI’s emphasized research areas as described in multiple notices of special interests (e.g. NOT-HL-20-815).