Physical and Neurocognitive Outcomes Among Children with Fetal Alcohol Spectrum Disorder Outcomes (FASD): The Contribution of Maternal Nutrition and Nutrigenetic Risk Factors

项目摘要/摘要 这个拟议的F32博士后奖学金的目标是为申请者提供一个 遗传流行病学和营养遗传学分析方面的多学科培训经验。这个 申请者将从事高级学术活动，以了解遗传和营养遗传学 对发育迟缓的易感性和严重程度的影响 构成胎儿酒精谱系障碍(FASD)的连续体。这样做的首要目标是 应用是表征母体营养、母婴遗传的作用 易感性，以及母亲饮食与基因的交互作用，因为它与孩子的身体状况有关 畸形、神经发育能力和FASD诊断。这个应用程序利用 关于以前收集的生物样本(循环血浆浓度)和遗传数据 来自南非西开普省的孕妇，她们的后代已经 出生后进行标准化的畸形学和神经发育评估。 这个项目将(1)确定母亲的营养状况是否会调节这种关系 酒精暴露与儿童生长发育、畸形和神经认知结果之间的关系； 制定与FASD诊断相关的多基因风险评分；以及(3)确定 胆碱相关的饮食与基因的相互作用部分解释了易感性和 FASD诊断的严重程度。培训计划的主要组成部分包括高级 教授遗传流行病学、营养基因组学理论和应用统计分析。 在此期间需要掌握的具体技能包括：(1)定量分析技能 复杂疾病遗传学；(2)营养遗传学数据分析高级培训；以及(3) 加强领导力和施展才干的能力。拟议的研究金将使这些 通过精心挑选的课程、研究经验、研讨会和研讨会来实现目标。 总体而言，这些将提供一个无与伦比的机会，以获得以前的高级技能 将这些方法和技术应用于一些重要但在很大程度上仍未得到解答的问题 FASD病因学。该应用程序为开展研究提供了丰富的培训环境 计划。拟议的研究计划将有助于申请者过渡到独立的 通过确立申请人在遗传学和营养遗传分析方面的专业知识和 应用这一专业知识来确定营养、遗传、营养遗传对 FASD诊断的敏感性和严重性，仍是一个广泛的研究领域 在FASD领域内没有特征。

Project Abstract/Summary The goal of this proposed F32 postdoctoral fellowship is to provide the applicant with a multi-disciplinary training experience in genetic epidemiology and nutrigenetics analysis. The applicant will engage in advanced scholarly activities to understand genetic and nutrigenetic influences on the susceptibility to, and severity of, developmental delays and traits that the constitute fetal alcohol spectrum disorders (FASD) continuum. The overarching aim of this application is to characterize the effect of maternal nutrition, maternal and child genetic predisposition, and maternal diet-by-genetic interaction as it relates to the child's physical dysmorphology, neurodevelopmental abilities, and FASD diagnosis. This application capitalizes on previously collected biological samples (circulating plasma concentrations) and genetic data from pregnant women in the Western Cape Province of South Africa whose offspring have been followed since birth with standardized dysmorphology and neurodevelopmental assessments. This project will (1) determine whether maternal nutrient status mediates the relationship between alcohol exposure and child growth, dysmorphology, and neurocognitive outcomes; (2) develop a polygenic risk score associated with FASD diagnosis; and (3) determine whether there is a choline-related diet-by-gene interaction which partially explains the susceptibility and severity of an FASD diagnosis. Key components of the training plan include advanced instruction in genetic epidemiology and nutrigenomic theory and applied statistical analysis. Specific skills to be mastered during this fellowship include: (1) quantitative analytic skills in the genetics of complex diseases; (2) advanced training in nutrigenetics data analysis; and (3) enhancement of leadership and grantsmanship skills. The proposed fellowship will enable these goals through carefully selected coursework, research experiences, seminars, and workshops. Collectively, these will provide an unparalleled opportunity to gain the advanced skills before applying the methods and techniques to important, yet largely unanswered questions about the etiology of FASD. This application provides a rich training environment to carry out the research plan. The proposed research plan will facilitate the applicant's transition into an independent investigator by establish the applicant's expertise in genetics and nutrigenetic analysis and applying this expertise to determining nutritional, genetic, nutrigenetic influences on the susceptibility and severity of an FASD diagnosis, an area of research remains vastly uncharacterized within the field of FASD.