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

存在疾病异质性的情况下先天性心脏缺陷的遗​​传和表观遗传关联的随机场建模

• 批准号: 10405321
• 负责人: Ming Li
• 金额: $ 5.03万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2023-01-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405321
• 关键词: Area; Biological; Biostatistical Methods; COVID-19; COVID-19 pandemic; Cardiovascular Diseases; Congenital Abnormality; Congenital Heart Defects; Counseling; Data Sources; Disease; Epidemiologist; Epigenetic Process; Etiology; Foundations; Future; Genetic; Genetic Models; Genetic Transcription; Goals; Institution; Interruption; Intervention; Journals; Life Style; Mentored Research Scientist Development Award; Methods; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Pathway interactions; Pediatric Cardiac Genomics Consortium; Peer Review; Population Study; Prevention; Principal Investigator; Process; Publications; Publishing; Research; Risk; Risk Factors; Sampling; Site; Time; Trans-Omics for Precision Medicine; Translational Research; United States National Institutes of Health; attributable mortality; base; career; disease heterogeneity; experience; infant morbidity/mortality; innovation; insight; interest; lifestyle factors; personalized intervention; predictive modeling; symposium

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).

项目摘要/摘要 该建议提交了NHLBI K01奖的延长，标题为“通用的随机现场建模 在存在疾病异质性的情况下，先天性心脏缺陷的表观遗传关联”。Mingli博士 是这项研究的主要研究者，属于该K01奖的最后一年（2018年1月1日 - 12/31/2021）。 在过去的一年中，Li博士的研究团队经历了大量的研究中断和其他 由于19号大流行而导致的行政责任。预计此扩展名将为李博士提供 完成正在进行的K01项目并成功过渡到未来R01研究的必要时间。 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，特别是先天性心脏缺陷（CHD）。在过去的三年中，李博士一直是 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 CHD。所提出的方法已应用于国家预防研究的样本 （NBDPS）是有史以来最大的基于多站点的人群研究。到目前为止，很重要 在同行评审期刊上发表了许多关键发现，取得了进展。其他发现 也在主要会议上介绍并提交出版物，但也经历了很大的延迟 由于COVID-19上断。这些结果为潜在的病理生理学和 导致CHD的病因学过程，也将成为Li博士提出额外建议的基础 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 其他现有NHLBI数据源的生物固化方法，例如小儿心脏基因组学财团 （PCGC）和精密医学的跨词（TopMed）； 2）进一步发展创新的生物统计学 基于遗传，表观遗传学，转录和 孕产妇的生活方式概况。这项研究的继续将整合NIH机构之间的数据源 （即NICHD和NHLBI），也可以为翻译研究提供指导 看觉咨询和干预措施。此类研究指示也与NHLBI的 如多个特殊利益通知所述（例如NOT-HL-20-815）所述的强调研究领域。

项目成果

PDGFRA gene, maternal binge drinking and obstructive heart defects.

• DOI: 10.1038/s41598-018-29160-9
• 发表时间: 2018-07-23
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Tang X;Eberhart JK;Cleves MA;Li J;Li M;MacLeod S;Nembhard WN;Hobbs CA
• 通讯作者: Hobbs CA

Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.

• DOI: 10.3390/genes14010180
• 发表时间: 2023-01-09
• 期刊: GENES
• 影响因子: 3.5
• 作者: Webber, Daniel M. M.;Li, Ming;MacLeod, Stewart L. L.;Tang, Xinyu;Levy, Joseph W. W.;Karim, Mohammad A. A.;Erickson, Stephen W. W.;Hobbs, Charlotte A. A.;Natl Birth Defects Prevention Study
• 通讯作者: Natl Birth Defects Prevention Study

Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease.

• DOI: 10.1186/s12863-021-00975-2
• 发表时间: 2021-06-10
• 期刊: BMC genomic data
• 影响因子: 1.9
• 作者: Li M;Lyu C;Huang M;Do C;Tycko B;Lupo PJ;MacLeod SL;Randolph CE;Liu N;Witte JS;Hobbs CA
• 通讯作者: Hobbs CA

Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci.

用于检测甲基化数量性状基因座的多性状多基因座关联的随机场建模。

• DOI: 10.1093/bioinformatics/btac443
• 发表时间: 2022
• 期刊: Bioinformatics (Oxford, England)
• 作者: Lyu,Chen;Huang,Manyan;Liu,Nianjun;Chen,Zhongxue;Lupo,PhilipJ;Tycko,Benjamin;Witte,JohnS;Hobbs,CharlotteA;Li,Ming
• 通讯作者: Li,Ming

Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.

• DOI: 10.3389/fgene.2021.657499
• 发表时间: 2021
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Huang M;Lyu C;Li X;Qureshi AA;Han J;Li M
• 通讯作者: Li M