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

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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.