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

(Provided by applicant): 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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
7U01AI090727-02
Application #
8098921
Study Section
Special Emphasis Panel (ZAI1-WFD-I (M3))
Program Officer
Dong, Gang
Project Start
2010-07-01
Project End
2015-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$434,192
Indirect Cost
Name
Johns Hopkins University
Department
Miscellaneous
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Liu, Xin; Hong, Xiumei; Tsai, Hui-Ju et al. (2018) Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy. Medicine (Baltimore) 97:e0043
Olapeju, Bolanle; Saifuddin, Ahmed; Wang, Guoying et al. (2018) Maternal postpartum plasma folate status and preterm birth in a high-risk US population. Public Health Nutr :1-11
Sherenian, Michael G; Singh, Anne M; Arguelles, Lester et al. (2018) Association of food allergy and decreased lung function in children and young adults with asthma. Ann Allergy Asthma Immunol 121:588-593.e1
Cheng, Tina L; Mistry, Kamila B; Wang, Guoying et al. (2018) Folate Nutrition Status in Mothers of the Boston Birth Cohort, Sample of a US Urban Low-Income Population. Am J Public Health 108:799-807
Raghavan, Ramkripa; Riley, Anne W; Volk, Heather et al. (2018) Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring. Paediatr Perinat Epidemiol 32:100-111
Tsai, Hui-Ju; Wang, Guoying; Hong, Xiumei et al. (2018) Early Life Weight Gain and Development of Childhood Asthma in a Prospective Birth Cohort. Ann Am Thorac Soc 15:1197-1204
Zhang, Mingyu; Mueller, Noel T; Wang, Hongjian et al. (2018) Maternal Exposure to Ambient Particulate Matter ?2.5 µm During Pregnancy and the Risk for High Blood Pressure in Childhood. Hypertension 72:194-201
Ji, Yuelong; Hong, Xiumei; Wang, Guoying et al. (2018) A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences. J Pediatr 199:124-131.e8
Mao, Guangyun; Nachman, Rebecca Massa; Sun, Qi et al. (2017) Individual and Joint Effects of Early-Life Ambient Exposure and Maternal Prepregnancy Obesity on Childhood Overweight or Obesity. Environ Health Perspect 125:067005
Wang, H; Xu, B P; Xu, R B et al. (2017) Joint effect of maternal plasma homocysteine and prepregnancy obesity on child blood pressure: a prospective birth cohort study. Int J Obes (Lond) 41:1447-1453

Showing the most recent 10 out of 39 publications