Food allergy (FA) is a growing clinical and public health problem in the U.S. and worldwide. The major obstacle in preventing and treating FA has been our incomplete understanding of its etiology and biological mechanisms. FA is believed to be a complex trait and determined by multiple environmental and genetic factors. A positive family history is a well-recognized predictor of allergic diseases. Our published and preliminary data underscore the important roles of genetic factors in FA. This proposal is a natural extension of our ongoing genome-wide association study (GWAS) of FA, which includes 1,000 Caucasian FA case-parents trios from Chicago. Genotyping was performed using the lllumina HumanOmni1-Quad BeadChip. Preliminary results from the GWAS are encouraging. This proposal will accomplish the following aims by utilizing two large, well-phenotyped study cohorts enrolled in Chicago and Boston, which were designed for large-scale molecular genetic epidemiologic studies of FA using a standard data collection protocol.
Aim 1 A. Confirmation study in an independent Caucasian sample: We plan to genotype promising SNPs/copy number variations (CNVs) identified from the GWAS and perform joint analysis in an independent sample of 1,200 Caucasian children using a case-control design: 600 Caucasian FA cases and 600 matched non-allergic controls from Chicago.
Aim I B. Replication Study in a Multiethnic Sample: For those SNPs/CNVs that have reached genome-wide significance (p<10-7) in the joint analysis from 1A, we plan to further genotype and test genetic association in an independent sample (n=1,800) using a nested case-control design: 600 FA cases and 1,200 matched non-allergic controls identified from the Boston Cohort. Of those, two thirds are African Americans and one third are Caucasians/Hispanics.
Aim 2. Fine Mapping to Search for Causative Variants: Based on the findings in Aim 1A and 1B, we will proceed to the discovery of novel SNPs/CNVs in the promising regions, by focused genotyping and association testing in the combined samples (n=6000 subjects), including the 1,000 FA trios and 600 FA case-control pairs from Chicago (n=4200) and 600 FA cases and 1200 controls from Boston (n=1800). This proposed study will be the first large-scale Post GWAS of FA in multi-ethnic U.S. populations. It has a high likelihood of success given the strong preliminary data, unique resources, and the team's track records. Findings from this study may transform our understanding of the causes of FA and inform future studies.

Public Health Relevance

Food allergy (FA) is a growing clinical and public health problem in the US and worldwide. The central focus of this proposal is to further replicate promising genetic variants identified by the ongoing genome-wide association study (GWAS) of FA and to search for causative genes of FA. This will be the first large-scale post GWAS of FA in multi-ethnic US populations. Findings from this study may help understand the causes of FA and eventually help develop effective strategies for prevention and treatment of FA.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI090727-05
Application #
8689888
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Dong, Gang
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Miscellaneous
Type
Schools of Public Health
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wang, Guoying; Hu, Frank B; Mistry, Kamila B et al. (2016) Association Between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations With Child Metabolic Health. JAMA Pediatr 170:e160845
Wang, Guoying; Johnson, Sara; Gong, Yiwei et al. (2016) Weight Gain in Infancy and Overweight or Obesity in Childhood across the Gestational Spectrum: a Prospective Birth Cohort Study. Sci Rep 6:29867
Li, Mengying; Fallin, M Daniele; Riley, Anne et al. (2016) The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics 137:e20152206
Makhija, Melanie M; Robison, Rachel G; Caruso, Deanna et al. (2016) Patterns of allergen sensitization and self-reported allergic disease in parents of food allergic children. Ann Allergy Asthma Immunol 117:382-386.e1
Walker, Sheila Ohlsson; Mao, Guangyun; Caruso, Deanna et al. (2016) Cardiovascular Risk Factors in Parents of Food-Allergic Children. Medicine (Baltimore) 95:e3156
Gupta, Ruchi S; Walkner, Madeline M; Greenhawt, Matthew et al. (2016) Food Allergy Sensitization and Presentation in Siblings of Food Allergic Children. J Allergy Clin Immunol Pract 4:956-62
Ladd-Acosta, Christine (2015) Epigenetic Signatures as Biomarkers of Exposure. Curr Environ Health Rep 2:117-25
Warren, Christopher M; Gupta, Ruchi S; Sohn, Min-Woong et al. (2015) Differences in empowerment and quality of life among parents of children with food allergy. Ann Allergy Asthma Immunol 114:117-25
He, Huan; Butz, Arlene; Keet, Corinne A et al. (2015) Preterm Birth with Childhood Asthma: The Role of Degree of Prematurity and Asthma Definitions. Am J Respir Crit Care Med 192:520-3
Hong, Xiumei; Hao, Ke; Ladd-Acosta, Christine et al. (2015) Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun 6:6304

Showing the most recent 10 out of 23 publications