Dietary Methyl Donors and Food Allergy Risk in the United States

美国的膳食甲基供体和食物过敏风险

• 批准号: 9242271
• 负责人: Emily Clarke McGowan
• 金额: $ 19.16万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-10 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9242271
• 关键词: 1 year old; 2 year old; 4 year old; Address; Affect; Allergic; Allergic Disease; Animal Model; Award; Birth; Blood; Boston; Carbon; Child; Childhood; Choline; Clinical; Collaborations; DNA; DNA Methylation; Data; Development; Diet; Disease; Doctor of Philosophy; Educational workshop; Environment; Epidemiologist; Epidemiology; Epigenetic Process; Exposure to; Folic Acid; Food; Food Hypersensitivity; Foundations; Future; Gene Expression; Genes; Genetic study; Goals; Health; Heritability; Homocysteine; Human; Hypersensitivity; Immunology; Infant; Intake; K-Series Research Career Programs; Knowledge; Lead; Life; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolism; Micronutrients; Modernization; Modification; Molecular; Nested Case-Control Study; Nutrient; Outcome; Pathway interactions; Pattern; Phenotype; Plasma; Play; Population; Population Study; Prevalence; Prospective cohort; Public Health; Public Health Schools; Regulatory T-Lymphocyte; Research; Resources; Risk; Risk Factors; Role; S-Adenosylhomocysteine; Sample Size; Sampling; Sampling Studies; Scientist; Serum Folate Level; Supplementation; T-Lymphocyte Subsets; Time; Training; Umbilical Cord Blood; United States; Vitamin B 12; Wood material; career; clinical investigation; cohort; epigenome; epigenomics; experience; genome-wide; high risk; in utero; infancy; meetings; methyl group; offspring; prenatal; prenatal exposure; skills; statistics; study population

PROJECT SUMMARY/ABSTRACT This career development award will provide Emily McGowan, MD with the skills, knowledge, and mentored research experience that are essential for an independent career as a clinician scientist in the field of allergy and immunology. Food allergy (FA) is a common childhood disease that appears to have increased in prevalence over the past two decades. The interplay between genes and the environment likely plays a key role in the development of FA, and DNA methylation is one possible mechanism by which environmental influences may affect gene expression. Several nutrients, including folate, vitamin B12, and choline, are involved in the one carbon metabolism pathway (OCMP), in which a methyl donor is transferred to DNA. In two separate cohorts, our group has shown an association between higher serum folate levels and the development of allergic sensitization, leading to our central hypothesis that differential exposure to folate, B12, and choline is associated with the development of food sensitization (FS) and FA, and that this is mediated by changes in DNAm. Dr. McGowan proposes to explore this hypothesis by examining 1) whether pre-natal or post-natal exposure to these OCMP micronutrients is independently associated with FS and FA; 2) whether differential exposure to these OCMP micronutrients is associated with DNA methylation; and 3) whether differentially methylated genes are associated with the development of FS and FA. In order to address these questions, Dr. McGowan will use two study populations: 1) a nested case-control study of children within the well-characterized Boston Birth Cohort (BBC) and 2) a new prospective cohort of 100 children at high risk for developing FA. Given the widespread exposure to methyl donors through formula and supplements in infancy, the results of this study could have major public health implications. In addition, this K23 award will provide Dr. McGowan with opportunities for advanced training in epidemiology, including the completion of a PhD in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health (JHBSPH). She will also pursue training to develop new skills in the analysis and interpretation of epigenomic data. Dr. McGowan plans to achieve these goals through formal coursework, workshops, national meetings, and mentored research. Her primary mentor for this award is Dr. Xiaobin Wang, a molecular epidemiologist who studies genetic and environmental predictors of childhood health. Her mentoring team further includes Drs. Robert Wood, Elizabeth Matsui, Corinne Keet, Daniele Fallin, and Kasper Hansen, experts in food allergy, epidemiology, epigenetics, and statistics. This training plan, and the data generated from this proposed project, will provide the foundation needed to successfully transition to the role of an independent clinician scientist studying the epidemiology and treatment of food allergy.

项目概要/摘要 该职业发展奖将为医学博士 Emily McGowan 提供技能、知识和指导 研究经验对于过敏领域临床科学家的独立职业至关重要 和免疫学。食物过敏 (FA) 是一种常见的儿童疾病，在儿童中似乎有所增加 近二十年来的盛行。基因和环境之间的相互作用可能起着关键作用 DNA 甲基化是 FA 发展中的作用，DNA 甲基化是环境影响的一种可能机制。 影响可能会影响基因表达。多种营养素，包括叶酸、维生素 B12 和胆碱， 参与单碳代谢途径 (OCMP)，其中甲基供体被转移到 DNA。分成两份 在不同的队列中，我们的研究小组发现较高的血清叶酸水平与 过敏性致敏的发展，导致我们的中心假设是叶酸、B12、 胆碱与食物过敏 (FS) 和 FA 的发生有关，并且这是由 DNAm 的变化。 McGowan 博士建议通过检查 1) 是否是产前或产前来探索这一假设。 产后接触这些 OCMP 微量营养素与 FS 和 FA 独立相关； 2）是否 这些 OCMP 微量营养素的差异暴露与 DNA 甲基化有关； 3) 是否 差异甲基化基因与 FS 和 FA 的发生有关。为了解决这些 为了回答这些问题，McGowan 博士将使用两个研究人群：1）针对儿童的巢式病例对照研究 特征明确的波士顿出生队列 (BBC) 和 2) 一个由 100 名高危儿童组成的新前瞻性队列 开发FA。鉴于婴儿期通过配方奶粉和补充剂广泛接触甲基供体， 这项研究的结果可能会对公共卫生产生重大影响。 此外，该 K23 奖项将为 McGowan 博士提供流行病学高级培训的机会， 包括在约翰霍普金斯大学彭博公立学院完成临床研究博士学位 健康（JHBSPH）。她还将接受培训，以发展分析和解释的新技能 表观基因组数据。麦高恩博士计划通过正式课程、研讨会、国家级会议来实现这些目标 会议并指导研究。她获得该奖项的主要导师是分子生物学家王晓斌博士。 研究儿童健康的遗传和环境预测因素的流行病学家。她的导师团队 还包括博士。罗伯特·伍德、伊丽莎白·松井、科琳·基特、丹尼尔·法林和卡斯帕·汉森， 食物过敏、流行病学、表观遗传学和统计学专家。该培训计划以及生成的数据 从这个拟议的项目中，将为成功过渡到一个角色提供所需的基础 研究食物过敏的流行病学和治疗的独立临床科学家。