Allergic rhinitis (AR) is an IgE-mediated inflammation of the upper airway that causes naso-ocular congestion and pruritus, rhinorrhea, and sneezing. Colloquially referred to as hay fever, seasonal allergies, and allergies, AR is one of the most common chronic diseases, affecting 10-30% of adults and 40% of children. The genetics of AR have been understudied relative to those of asthma. We hypothesize that there are significant genetic determinants of AR, that these genes can be identified using integrative genomic approaches in at-risk populations, and that these genes interact in networks to regulate allergen-induced cytokine production in AR patients. We will test this hypothesis via three specific aims. First, we will perform a genome-wide analysis for single nucleotide polymorphisms (SNP) that alter risk for allergic rhinitis and replicate our findings in two independent cohorts. Second, we will pilot and implement a nasal epithelium collection protocol in asthmatic subjects, obtain gene expression profiles using this nasal epithelium resource, and perform integrative genomic analysis of allergic rhinitis using expression data from nasal epithelium and CD4+ lymphocytes. Third, we will perform luciferase reporter assays and measure allergen-induced cytokine proliferation to validate the biologic relevance of identified genetic variants, and model networks to integrate our experimental data within the context of immunologic pathways. We anticipate that functional variants identified from this proposal will elucidate immunologic pathways and define targets for disease prediction and therapeutic intervention. In addition to its scientific relevance, the proposed project outlines a career development plan that will train the principal investigator to become an independent investigator in the genetics and genomics of allergic disease.

Agency
National Institute of Health (NIH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI093538-05
Application #
8658801
Study Section
Transplantation Biology &Immunology-2 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Genetics
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Bunyavanich, Supinda; Schadt, Eric E (2015) Systems biology of asthma and allergic diseases: a multiscale approach. J Allergy Clin Immunol 135:31-42
Bunyavanich, Supinda; Schadt, Eric E; Himes, Blanca E et al. (2014) Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis. BMC Med Genomics 7:48
Bunyavanich, Supinda; Rifas-Shiman, Sheryl L; Platts-Mills, Thomas A et al. (2014) Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children. J Allergy Clin Immunol 133:1373-82
Bunyavanich, Supinda; Rifas-Shiman, Sheryl L; Platts-Mills, Thomas A E et al. (2014) Peanut allergy prevalence among school-age children in a US cohort not selected for any disease. J Allergy Clin Immunol 134:753-5
Bunyavanich, Supinda; Donovan, Marilyn A; Sherry, Jacqueline M et al. (2013) Immunotherapy for mouse bite anaphylaxis and allergy. Ann Allergy Asthma Immunol 111:223-4