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.

项目总结/摘要 这个职业发展奖将提供艾米丽麦高恩，医学博士的技能，知识，并指导 研究经验是必不可少的独立职业生涯作为一个临床科学家在过敏领域 和免疫学。食物过敏（FA）是一种常见的儿童疾病， 在过去的二十年里，基因和环境之间的相互作用可能起着关键作用 在FA的发展中起作用，DNA甲基化是环境影响FA的一种可能机制。 影响可能会影响基因表达。一些营养素，包括叶酸，维生素B12和胆碱， 参与单碳代谢途径（OCMP），其中甲基供体转移到DNA。在两 我们的研究小组已经表明，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，即不同暴露于叶酸，B12， 胆碱与食物致敏（FS）和FA的发展有关，这是由 DNA的变化。麦高恩博士建议通过检查1）是否产前或 出生后暴露于这些OCMP微量营养素与FS和FA独立相关; 2）是否 这些OCMP微量营养素的不同暴露与DNA甲基化有关;以及3）是否 差异甲基化基因与FS和FA的发生相关。为了解决这些 McGowan博士将使用两个研究人群：1）对儿童进行嵌套病例对照研究， 波士顿出生队列（BBC）和2）一个新的前瞻性队列的100名儿童的高风险， 发展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，K23奖项还将为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彭博公共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 表观基因组数据。麦高恩博士计划通过正式的课程，研讨会，国家 会议和指导研究。她获得这个奖项的主要导师是王晓斌博士， 研究儿童健康的遗传和环境预测因素的流行病学家。她的指导团队 还包括罗伯特·伍德博士、伊丽莎白·松井博士、科琳·基特博士、丹尼尔·弗林博士和卡斯珀·汉森博士， 食物过敏、流行病学、表观遗传学和统计学专家。这个培训计划，以及生成的数据 从这个拟议的项目，将提供成功过渡到一个角色所需的基础， 研究食物过敏的流行病学和治疗的独立临床科学家。