# High-resolution characterization of human leukocyte antigen genes in diverse populations to study the genetics of food allergy

> **NIH NIH R56** · HENRY FORD HEALTH SYSTEM · 2022 · $449,999

## Abstract

Food allergies are common, costly, and potentially life-threatening. Epidemiologic studies suggest prevalence
is growing, particularly among minority populations. Twin studies estimate that food allergies are highly
heritable (>80%), underscoring the importance of genetic causes. To date, there has been only a few
genome-wide association studies of food allergy and none with African Americans or Latinos in the discovery
set. Moreover, the phenotypes used in these studies have been inconsistent. Despite these issues, there
have been some consistent findings, such as repeated associations with human leukocyte antigen (HLA)
genes. This is not altogether surprising given the role that HLA proteins play in presenting antigens to
effectors cells, resulting in either tolerance or sensitization. However, our ability to identify causal variants in
HLA genes is hampered by the structural complexity of the major histocompatibility complex (MHC) region (i.e.,
an exceptionally high degree of polymorphism, numerous pseudogenes, and long-range linkage
disequilibrium). In this application, we take a multifaceted approach to better understanding food sensitization,
food allergy disparities, and the underlying risk factors. We have assembled three large, diverse study cohorts
(combined n=12,882): the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity
(SAPPHIRE); the Study of African Americans, Asthma, Genes & Environment (SAGE); and the Genes-
Environments & Admixture in Latino Americans (GALA II). These multi-ethnic cohorts have a wealth of
existing socio-environmental exposure data and high-depth short-read whole-genome sequencing (WGS). In
Aim 1, we will utilize IgE arrays to broadly characterize allergic sensitization for 94 different foods and 77 food
allergen components. These data will allow us to identify differences in food sensitization between population
groups (i.e., African Americans, Latinos [Mexicans and Puerto Ricans], and European Americans) and to
assess the relationship between socio-environmental exposures (e.g., air pollution, tobacco smoke,
neighborhood characteristics, and perinatal events) and food allergen sensitization. In Aim 2, we will leverage
the large and diverse study population, existing WGS, and IgE sensitization data from Aim 1 to investigate for
genetic variants associated with any food sensitization and sensitization to specific common food allergens
(e.g., peanut, seafood, tree nut, dairy, and egg). Associations will be replicated in a large pediatric cohort from
the Children’s Hospital of Philadelphia. To overcome the aforementioned challenges of the MHC region, in
Aim 3 we propose a novel approach, which exploits the benefits of short-read DNA sequencing (high fidelity)
and recent advances in ultra-long-read DNA sequencing. The resulting de novo, high-resolution assemblies of
the MHC region will be used to look for HLA variants associated with food sensitization in a large sample of
African America...

## Key facts

- **NIH application ID:** 10665162
- **Project number:** 1R56AI165903-01A1
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **Principal Investigator:** Keoki Williams
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $449,999
- **Award type:** 1
- **Project period:** 2022-09-12 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665162

## Citation

> US National Institutes of Health, RePORTER application 10665162, High-resolution characterization of human leukocyte antigen genes in diverse populations to study the genetics of food allergy (1R56AI165903-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10665162. Licensed CC0.

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