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Genetic Determinants of Food Allergy Among Pediatric Populations

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Food allergy is a complex disease of substantial public health concern, affecting ~7% of the pediatric population, and is a common cause of anaphylaxis. The prevalence of food-induced anaphylaxis is rising, accounting for one-third to one-half of anaphylaxis cases globally and resulting in ~150 deaths in the U.S. annually. Food allergy represents a variety of clinical manifestations attributed to adverse immunologic responses to food proteins, with the most common of food allergic disorders being those mediated by food-specific IgE antibodies. Peanut allergy accounts for the majority of severe and deadly food allergic reactions, and allergies to peanut are typically life-long. Although studies focusing on the genetic basis for IgE-mediated food allergy have been seriously limited, heritability studies and several candidate gene studies suggest that, similar to the 'atopic triad'diseases of asthma, allergic rhinitis (AR), and atopic dermatitis (AD), susceptibility to IgE-mediated food allergy is likely determined by multiple genes with major and minor influences impacted by gene-gene and gene-environment interactions. The high rate of co-morbidity between food allergy and asthma, AR and AD suggests that some genetic determinants may generically confer risk to all four traits. We hypothesize that there are genetic determinants which are unique to food allergy and distinct from those loci associated with atopy. We further hypothesize that certain genetic determinants are associated with a specific immune response to specific foods (e.g., peanut allergy). A major goal of the Consortium of Food Allergy Research (CoFAR) is to collect biological samples and extensive phenotypic data on food allergic infants with an aim to track the development of peanut allergy;thus, this program offers a unique opportunity to establish a robust DNA repository for extensive genetic epidemiology studies. This cohort, combined with existing datasets of asthma, atopy, and AD in the PI's laboratory, renders an ideal opportunity for genetic studies on food allergy. The genome-wide association approach has proved to be both feasible and useful in terms of elucidating solid candidate genes for complex traits, especially those for which there is limited a priori knowledge regarding candidate genes or loci. By screening dense panels of markers representing the entire genome, many more risk variants will be identified than what could be accomplished using conventional, candidate gene-based studies. In this Exploratory/Developmental Research R21 Grant application, we will (1) develop the research infrastructure for a future case-control-based, genome-wide association study on IgE-mediated food allergy in general and peanut allergy in particular, by establishing a DNA repository of 2,000 samples from patients of European and African descent;and (2) perform exploratory genetic association studies between food allergy susceptibility and a limited set of candidate genes for food allergy. Success in this application will provide the essential preliminary data and infrastructure for a larger grant application for a genome-wide association study on food allergy.

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