Genetic ancestry differences in IgE- mediated peanut allergy in African Americans

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Abstract The burden of food allergy (FA) is disproportionately high among minority children, in particular the prevalence of FA is 4 times higher in African American (AA) than European American (EA) children. Peanut allergy (PA) is the most common and serious form of FA. As in FA in general, PA exhibits the same racial disparity between AA and EA. Although there is a general consensus about the role of genetic ancestry in PA risk, the extent to which ancestry contributes or explains racial disparities remains largely unknown. Our long-term goal is to determine genetic ancestry determinants that contribute to total and peanut specific IgE disparities in admixed AA children. Our overall objective is to determine to what extent peanut specific IgE risk is determined by genetic ancestry in AA admixed individuals with varying African ancestry proportion. Our well-phenotyped PA cohorts with collected DNA samples, and high-density genome-wide Multi-Ethnic Global Array (MEGA) that contains SNP sets tailored towards admixed ancestry presents a unique opportunity to identify ancestry-specific PA risk variants. We hypothesize that genetic variants with large allele frequency differences between African and European ancestry population may be partly responsible for the current difference in PA risk. Two Specific Aims are proposed to test our hypothesis and achieve our proposed plan: Aim 1) Determine the genetic ancestry and conduct admixture mapping using multi-ethnic genotyping array; and Aim 2) Replicate the most promising variants in AM peak regions using independent replication cohorts. The proposed study is highly significant (given the high burden of PA among AA children) and highly innovative (it is the first admixture analysis) to unravel genetic ancestry-specific risk variants associated with PA. Most importantly, the results will be on minority population and will contribute to our knowledge and to the early prediction, diagnosis and treatment of PA—a road map towards precision diagnosis. We therefore believe that this study along with future studies will uncover fundamental information about whether genetic ancestry can affect PA risk and prediction, thereby reducing the burden of PA on patients and their families and improving their quality of life. 1