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

胎儿酒精谱系障碍 (FASD) 儿童的身体和神经认知结果：母亲营养和营养遗传风险因素的影响

• 批准号: 10537692
• 负责人: Julie Hasken
• 金额: $ 7.17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10537692
• 关键词: Address; Adult; Adverse effects; Affect; Alcohol dependence; Alcohols; Alleles; Animal Model; Animals; Area; Betaine; Biological; Birth; Calcium; Candidate Disease Gene; Carbon; Child; Choline; Communities; Complex; Copper; Coupled; Custom; Data; Data Analyses; Data Set; Development; Developmental Delay Disorders; Diagnosis; Diet; Dietary Intervention; Dietary intake; Disease; Docosahexaenoic Acids; Dysmorphology; Educational workshop; Eicosapentaenoic Acid; Environment; Equation; Ethanol Metabolism; Etiology; Face; Fatty Acids; Fellowship; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Development; Folic Acid; Frequencies; Future; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genomics; Genotype; Goals; Growth; Growth and Development function; Homocysteine; Individual; Infant; Instruction; Intervention; Iron; Leadership; Longitudinal cohort; Measurement; Mediating; Metabolism; Methods; Micronutrients; Modeling; Mothers; Neuraxis; Neurocognitive; Neurocognitive Deficit; Neurological outcome; Nutrient; Nutritional; Nutritional status; Omega-3 Fatty Acids; Outcome; Outcomes Research; Pathway interactions; Phenotype; Plasma; Population; Predisposition; Pregnancy; Pregnant Women; Prevalence; Province; Regulator Genes; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Severities; Single Nucleotide Polymorphism; South Africa; Standardization; Statistical Data Interpretation; Techniques; Testing; Training; United States; Variant; Vitamin B6; Zinc; adverse outcome; alcohol consumption during pregnancy; alcohol exposure; alpha-Linolenic Acid; bead chip; cohort; craniofacial; design; dietary; dimethylglycine; docosapentaenoic acid; experience; frontier; gene interaction; genetic epidemiology; genetic risk factor; genome wide association study; individual variation; innovation; insight; micronutrient deficiency; mother nutrition; multi-ethnic; multidisciplinary; neurobehavioral; novel; nutrition related genetics; nutritional genomics; offspring; phenotypic data; polygenic risk score; population based; postnatal; precision nutrition; prenatal; preventive intervention; protective allele; recruit; risk variant; saliva sample; skeletal; skills; theories; trait; virtual

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.

项目摘要/总结 拟议的 F32 博士后奖学金的目标是为申请人提供 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 申请人将从事高级学术活动以了解遗传和营养遗传学 影响发育迟缓和特征的易感性和严重程度 构成胎儿酒精谱系障碍（FASD）的连续体。本次活动的总体目标是 应用是表征孕产妇营养、孕产妇和儿童遗传的影响 易感性和母亲饮食与遗传的相互作用，因为它与孩子的身体有关 畸形、神经发育能力和 FASD 诊断。该应用程序大写 基于先前收集的生物样本（循环血浆浓度）和遗传数据 来自南非西开普省的孕妇，其后代已被 从出生起就进行标准化的畸形学和神经发育评估。 该项目将 (1) 确定母体营养状况是否介导这种关系 酒精暴露与儿童生长、形态畸形和神经认知结果之间的关系； (2) 制定与 FASD 诊断相关的多基因风险评分； (3) 确定是否 存在与胆碱相关的饮食基因相互作用，这部分解释了易感性和 FASD 诊断的严重程度。培训计划的关键组成部分包括高级 遗传流行病学和营养基因组学理论以及应用统计分析的教学。 在此研究期间需要掌握的具体技能包括：（1）定量分析技能 复杂疾病的遗传学； (2)营养遗传学数据分析高级培训；和（3） 提高领导和资助技能。拟议的研究金将使这些 通过精心挑选的课程、研究经验、研讨会和讲习班来实现目标。 总的来说，这些将为获得高级技能提供无与伦比的机会 将这些方法和技术应用于重要的、但在很大程度上尚未得到解答的问题 FASD 的病因学。该应用程序提供了丰富的培训环境来开展研究 计划。拟议的研究计划将有助于申请人转变为独立的研究计划 研究者通过建立申请人在遗传学和营养遗传学分析方面的专业知识和 应用这些专业知识来确定营养、遗传、营养遗传对 FASD 诊断的易感性和严重程度，这一领域的研究仍很广泛 在 FASD 领域内没有特征。