Dietary Methyl Donors and Food Allergy Risk in The United States

PROJECT SUMMARY/ABSTRACTThis career development award will provide Emily McGowan, MD with the skills, knowledge, and mentoredresearch experience that are essential for an independent career as a clinician scientist in the field of allergyand immunology. Food allergy (FA) is a common childhood disease that appears to have increased inprevalence over the past two decades. The interplay between genes and the environment likely plays a keyrole in the development of FA, and DNA methylation is one possible mechanism by which environmentalinfluences may affect gene expression. Several nutrients, including folate, vitamin B12, and choline, areinvolved in the one carbon metabolism pathway (OCMP), in which a methyl donor is transferred to DNA. In twoseparate cohorts, our group has shown an association between higher serum folate levels and thedevelopment 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 bychanges in DNAm. Dr. McGowan proposes to explore this hypothesis by examining 1) whether pre-natal orpost-natal exposure to these OCMP micronutrients is independently associated with FS and FA; 2) whetherdifferential exposure to these OCMP micronutrients is associated with DNA methylation; and 3) whetherdifferentially methylated genes are associated with the development of FS and FA. In order to address thesequestions, Dr. McGowan will use two study populations: 1) a nested case-control study of children within thewell-characterized Boston Birth Cohort (BBC) and 2) a new prospective cohort of 100 children at high risk fordeveloping 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 PublicHealth (JHBSPH). She will also pursue training to develop new skills in the analysis and interpretation ofepigenomic data. Dr. McGowan plans to achieve these goals through formal coursework, workshops, nationalmeetings, and mentored research. Her primary mentor for this award is Dr. Xiaobin Wang, a molecularepidemiologist who studies genetic and environmental predictors of childhood health. Her mentoring teamfurther 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 generatedfrom this proposed project, will provide the foundation needed to successfully transition to the role of anindependent clinician scientist studying the epidemiology and treatment of food allergy.