Shared Genetic Etiology Between Eoe and Other Allergic Diseases

Abstract

RATIONALE: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease characterized by eosinophils in the esophagus. Patients with EoE often have other allergic diseases such as asthma (AS), allergic rhinitis (AR), and atopic dermatitis (AD), and less frequently celiac disease or Crohn's disease. METHODS: Using the results of our recently published genome-wide association study, we performed a permutation-based enrichment analysis on EoE risk loci to identify individual shared loci and the global enrichment of loci that reached genome-wide significant association in other diseases. RESULTS: We identified four loci that were shared between EoE and at least one of the assessed phenotypes. For example, there was strong association (p<10-7, all diseases) with EoE, AS, AR, AD, and Crohn's disease at 11q13 which encodes LRRC32 and C11orf30. Furthermore, using EoE risk loci p<10-4, we identified significant enrichment for other disease risk loci (p<5x10-8) including AS, AR, AD, and celiac disease. No enrichment was found for Crohn's disease, rheumatoid arthritis or ankylosing spondylitis loci. Of the genes in loci with shared association between EoE and AS, AR, Celiac, or AD, 45.1% and 6.1% were expressed and dysregulated in the esophageal biopsies of EoE patients, respectively, which are both significantly higher percentages than expected by chance (p<10-4). CONCLUSIONS: We identified EoE risk loci that are shared with 5 related diseases, with a major common locus at 11q13. Shared EoE-risk loci are expressed and dysregulated in esophagi of patients with EoE. These results imply shared etiology between EoE and other allergic related diseases as well as celiac disease.