Genetic and Environmental Determinants of Food Allergy
Keet, Corinne Allison
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Introduction: This thesis attempts to answer several questions about the epidemiology of pediatric allergy, including (1) the prevalence of pediatric food allergy in the United States and its changes over time, (2) whether variation in serum folate and vitamin D levels is associated with incident sensitization, and (3) whether common genetic variants interact with season of birth to affect the risk of food allergy. Methods: The thesis follows a three paper format, containing the following sections: (1) a systematic review and meta-analysis/meta-regression of food allergy prevalence in the United States, (2) a nested case-control study of incident mouse allergy in laboratory workers, examining associations with vitamin D and folate, and (3) a genome wide association study looking for possible interactions between fall season of birth and genetic markers influencing risk of food allergy in a family based cohort. Results: We found the prevalence of self-reported food allergy has increased in the United States in recent decades, and this increase has been most pronounced among Non-Hispanic Blacks; higher folate, but not vitamin D, levels are associated with a higher risk of incident sensitization to a selected allergen; and common genetic markers in or around the PBRM1 gene interact with Fall season of birth to influence the risk of food allergy. Conclusions: These findings suggest (1) environmental causes should be sought for the increased prevalence of food allergy in the United States,;(2) folic acid supplementation and fortification may be one environmental factor contributing to increased risk of sensitization; and (3) genetic variants in or around the PBRM1 gene may interact with another environmental factor, fall season of birth, to influence the development of food allergy. Together, these findings suggest several hypotheses for further exploration to understand the genetic and environmental causes of food allergy.