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. PROJECT NARRATIVE /

Public Health Relevance

Allergic rhinitis is one of the most common chronic diseases in children and adults.2 Allergic rhinitis is associated with decreased work productivity,4 poor school attendance,4 increased asthma severity,1 and higher rates of asthma-related hospitalization.5 We will use genetic and genomic approaches to identify novel disease-modifying genetic variants in allergic rhinitis that may be targeted for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
7K08AI093538-03
Application #
8535350
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2011-07-01
Project End
2016-05-31
Budget Start
2012-09-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$104,146
Indirect Cost
$7,624
Name
Icahn School of Medicine at Mount Sinai
Department
Genetics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Sann, Julia; Bunyavanich, Supinda; Wang, Julie (2016) Epinephrine autoinjector prescribing patterns in an urban pediatric population. J Allergy Clin Immunol Pract 4:989-90
Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander et al. (2016) Early-life gut microbiome composition and milk allergy resolution. J Allergy Clin Immunol 138:1122-1130
Bunyavanich, Supinda; Rifas-Shiman, Sheryl L; Platts-Mills, Thomas A et al. (2016) Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization. J Allergy Clin Immunol 137:1063-70.e1-2
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; Celedón, Juan C (2015) Use of inhaled corticosteroids among Hispanics in the United States. Ann Am Thorac Soc 12:241-2
Sordillo, Joanne E; Scirica, Christina V; Rifas-Shiman, Sheryl L et al. (2015) Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children. J Allergy Clin Immunol 135:441-8
Lee, Tricia D; Gimenez, Gustavo; Grishina, Galina et al. (2015) Profile of a milk-allergic patient who tolerated partially hydrolyzed whey formula. J Allergy Clin Immunol Pract 3:116-8
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; 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; 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

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