Genetic and Environmental Determinants of Food Allergy

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

Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy

We previously reported results of a randomized, placebo-controlled study of egg oral immunotherapy (eOIT), in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report results of treatment through 4 years and long-term follow-up

Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10 -8) and rs9275596 (P=6.8 × 10 -10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (

Associations between serum per- and polyfluoroalkyl substances and asthma morbidity in the National Health and Nutrition Examination Survey (2003-18)

Background: Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals widely used in manufacturing and are highly resistant to degradation, so they accumulate in the environment. Serum concentrations of these so-called forever chemicals have been associated with impairment of innate and adaptive immune responses. The relationship between serum PFAS levels and asthma morbidity has not been studied. Objective: We tested the association between serum PFAS concentration and asthma exacerbations. Methods: We performed secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES, 2003-18). We fit multivariable logistic regression models to estimate odds ratios and 95% CIs for asthma exacerbation in the prior 12 months, given serum concentrations of PFAS. Models were adjusted for relevant covariates. Results: Of 1101 participants with self-reported current asthma and available serum PFAS data, we observed that higher serum perfluorooctanoic and perfluorodecanoic acids were associated with greater odds of asthma attacks in the previous 12 months (respectively, adjusted odds ratio 1.16, 95% CI 1.01, 1.33; and adjusted odds ratio 1.21, 95% CI 1.03, 1.43). After stratification by age, the association between perfluorooctanoic acid and asthma attacks was significant in the 12-18-year-old group only (adjusted odds ratio 1.56, 95% CI 1.06, 2.31). No significant relationships were observed between PFAS and asthma-related emergency department visits. After correction for multiple comparison testing, none of the associations reached the threshold of significance. Conclusion: The role of these bioaccumulative forever chemicals in susceptibility to asthma attacks warrants further examination in longitudinal studies