Aims: The overall goal of this project is to identify and characterize novel genetic and epigenetic risk factors of food allergen sensitization by integrating three complementary approaches in a study population of asthmatics. The focus on asthmatics will reduce phenotypic heterogeneity and enhance the strength of genetic and epigenetic associations. First, we propose to use existing genome-wide and epigenome-wide association data in a sample of ~1,200 asthmatics from the Asthma Biorepository for Integrative Genomic Research (ABRIDGE, PI: Benjamin Raby, Harvard) to evaluate associations with food sensitization, as defined by specific immunoglobulin IgE (sIgE) measurements to 6 major food allergens and self-reported history of food allergic reactions. Second, we aim to integrate these association results with genome-wide expression data to identify a set of candidate genes having associated genetic and/or epigenetic variants and showing altered expression as related to food sensitization. Lastly, we propose to evaluate the candidate gene associations in independent study populations. We are seeking to include ALSPAC in this replication effort.

Hypotheses: Statistically significant associations of genetic and epigenetic variants will be identified for food sensitization in asthmatics from ABRIDGE, and these variants will be located within genes that show altered expression as related to food sensitization. The identified genetic and epigenetic risk factors will also have statistically significant associations in independent study populations of asthmatics.