Integrative metabolomic characterization of ADHD and asthma comorbidity

ADHD 和哮喘合并症的综合代谢组学特征

• 批准号: 10041169
• 负责人: Su Hee Chu
• 金额: $ 17.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10041169
• 关键词: Achievement; Adolescence; Adult; Area; Asthma; Attention deficit hyperactivity disorder; Awareness; Behavior Disorders; Biochemical; Biological; Biological Markers; Child; Childhood; Childhood Asthma; Clinical; Communication Research; Communities; Complex; Data; Diagnosis; Disease; Doctor of Philosophy; Educational process of instructing; Ensure; Environmental Exposure; Epidemiologist; Epidemiology; Etiology; Formulation; Genetic; Genetic Variation; Goals; Hospitals; Hyperactive behavior; Individual; Joints; Libraries; Link; Literature; Longevity; Longitudinal Studies; Lung diseases; Machine Learning; Mediating; Mediation; Mediator of activation protein; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Molecular; Multiomic Data; Neurodevelopmental Disorder; Pathway interactions; Patients; Phenotype; Prevalence; Process; Program Development; Prospective Studies; Prospective cohort; Public Health; Reporting; Research; Research Design; Research Personnel; Respiration Disorders; Risk; Specific qualifier value; Sphingolipids; Statistical Methods; System; Techniques; Testing; Training; Tryptophan; Validation; Variant; Vitamin D; Woman; antenatal; asthmatic; asthmatic patient; biological systems; career; career development; cohort; comorbidity; experience; genetic testing; genetic variant; high risk; improved; inattention; insight; medical schools; metabolic phenotype; metabolic profile; metabolomics; method development; multiple omics; novel; predictive modeling; programs; prospective; psychogenetics; research and development; respiratory; screening; skills; small molecule; statistics; success; theories

PROJECT SUMMARY/ABSTRACT Su H. Chu, PhD, MS is a biostatistician and molecular epidemiologist with strong and substantial commitments to integrative omic research in respiratory and neurodevelopmental disease. Her career objective is to become an independent investigator with expertise in developing and applying novel statistical methods and multiomic network approaches that facilitate mechanistic understanding of the intersection of respiratory and neurodevelopmental disease. This proposal combines Dr. Chu’s extensive training in integrative omic methods development, along with her experience in genetic and metabolomic research, to examine the integrative metabolomic etiology of asthma and attention-deficit/hyperactivity disorder overlap (AAO). A wealth of epidemiological literature has revealed with remarkable consistency that asthmatic patients are at greater risk for ADHD, and vice versa, with a number of longitudinal studies of childhood asthma indicating excess risk of ADHD in adolescence and adulthood. However, no studies have directly interrogated the biological mechanisms by which these conditions may be related. The central hypothesis of this proposal is that childhood asthma and ADHD share both common and distinct dysregulated metabolic processes, some of which may have drivers that are genetic in origin. This will be explored using existing genetic and metabolomic data from the Childhood Asthma Management Program (CAMP), the Vitamin D Antenatal Asthma Reduction Trial (VDAART), and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC), three large prospective cohorts of children with extensive longitudinal phenotyping and multiple omic data types, by identifying metabolites and metabolic profiles associated with AAO (aim 1), constructing multiomic models and features that characterize dysregulated metabolic processes and their upstream drivers in AAO (aim 2), and validation and replication of all findings (aim 3). As Dr. Chu completes these aims, her career development program will facilitate the achievement of her primary training goals: 1) increase clinical understanding of ADHD and asthma diagnosis and treatment; 2) gain a nuanced understanding of best methods for, and practical experience in, the biological and statistical integration of genetic and metabolomic data; 3) develop skills in machine learning and integrative network methods for multiomic analysis; 4) strengthen current areas of experience to stay on the cutting edge of new analytic and study design techniques; and 5) enhance skills in mentorship, teaching, and the responsible conduct and communication of research. The support of a diverse mentoring team comprised of world experts in the fields of asthma and psychiatric genetics, metabolomics, integrative omics, and statistics, along with her strong quantitative training and the vibrant intellectual community of Harvard Medical School and the Brigham and Women’s Hospital, ensure the success of this proposal. Finally, this research will use state-of-the-art multiomic techniques to lay the initial groundwork for understanding the pathobiology of asthma and ADHD comorbidity, a major and well-established public health concern, from which new research programs will emerge.

项目总结/摘要 苏·H Chu博士，MS是一名生物统计学家和分子流行病学家，具有强大而实质性的承诺 呼吸系统和神经发育疾病的综合组学研究。她的职业目标是成为 一位独立的研究者，在开发和应用新的统计方法和多组学方面具有专业知识。 网络的方法，促进机械的理解，呼吸和 神经发育疾病这个建议结合了朱博士在综合组学方法方面的广泛训练， 发展，沿着她在遗传和代谢组学研究的经验，以检查整合 哮喘和注意缺陷多动障碍重叠（AAO）的代谢组学病因。丰富的 流行病学文献显示，哮喘患者有更大的风险， 对于ADHD，反之亦然，一些儿童哮喘的纵向研究表明， ADHD在青春期和成年期然而，没有研究直接询问生物学机制， 这些条件可能是相关的。这项建议的中心假设是，儿童哮喘和 ADHD有共同的和不同的代谢过程失调，其中一些可能有驱动因素， 都是遗传的这将利用现有的遗传和代谢组学数据进行探索， 哮喘管理计划（CAMP）、维生素D治疗哮喘减少试验（VDAART）和 2010年哥本哈根儿童哮喘前瞻性研究（COPSAC），三个大型前瞻性队列， 儿童广泛的纵向表型和多种组学数据类型，通过识别代谢物和 与AAO相关的代谢谱（目的1），构建多组模型和特征， AAO中失调的代谢过程及其上游驱动因素（目的2），以及验证和复制 所有调查结果（目标3）。随着朱博士完成这些目标，她的职业发展计划将促进 实现她的主要培训目标：1）增加对ADHD和哮喘诊断的临床理解 2）获得最佳方法的细致入微的理解，并在生物学的实践经验， 遗传和代谢组学数据的统计整合; 3）发展机器学习和整合的技能 多组学分析的网络方法; 4）加强现有的经验领域， 新的分析和研究设计技术; 5）提高指导，教学和责任的技能 研究的开展和交流。由世界各地专家组成的多元化指导团队的支持 在哮喘和精神病遗传学、代谢组学、整合组学和统计学领域，沿着她 强大的定量培训和充满活力的知识界的哈佛医学院和布里格姆 和妇女医院，确保这一建议的成功。最后，本研究将使用最先进的 多组学技术为理解哮喘和ADHD的病理生物学奠定了初步基础 科摩罗，一个主要的和完善的公共卫生问题，从新的研究项目将出现。