Genome-wide admixture and association analysis identifies African ancestry–specific risk loci of eosinophilic esophagitis in African Americans

Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) investigators

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease, is linked to multiple genetic risk factors, but studies have focused on populations of European ancestry. Few studies have assessed Black or African American (AA) populations for loci involved in EoE susceptibility. Objective: We performed admixture mapping (AM) and genome-wide association study (GWAS) of EoE using participants from AA populations. Methods: We conducted AM and GWAS of EoE using 137 EoE cases and 1465 healthy controls from the AA population. Samples were genotyped using molecular evolutionary genetics analysis (MEGA). Genotype imputation was carried out with the Consortium on Asthma Among African-Ancestry Populations in the Americas (CAAPA) reference panel using the Michigan Imputation Server. Global and local ancestry inference was carried out, followed by fine mapping and RNA sequencing. After quality control filtering, over 6,000,000 variants were tested by logistic regression adjusted for sex, age, and global ancestry. Results: The global African ancestry proportion was found to be significantly lower among cases than controls (0.751 vs 0.786, P = .012). Case-only AM identified 3 significant loci (9p13.3, 12q24.22-23, and 15q11.2) associated with EoE, of which 12q24.22-23 and 9p13.3 were further replicated in the case–control analysis, with associations observed with African ancestry. Fine mapping and multiomic functional annotations prioritized the variants rs11068264 (FBXW8) and rs7307331 (VSIG10) at 12q24.23 and rs2297879 (ARHGEF39) at 9p13.3. GWAS identified 1 genome-wide significant locus at chromosome 1p22.3 (rs17131726, DDAH1) and 10 other suggestive loci. Most GWAS variants were low-frequency African ancestry–specific variants. RNA sequencing revealed that esophageal DDAH1 and VSIG10 were downregulated and ARHGEF39 upregulated among EoE cases. Conclusions: GWAS and AM for EoE in AA revealed that African ancestry–specific genetic susceptibility loci exist at 1p22.3, 9p13.3, and 12q24.23, providing evidence of ancestry-specific inheritance of EoE. More independent genetic studies of different ancestries for EoE are needed.

Original languageEnglish (US)
Pages (from-to)1337-1350
Number of pages14
JournalJournal of Allergy and Clinical Immunology
Issue number5
StatePublished - May 2023


  • African American
  • Eosinophilic esophagitis
  • admixture mapping
  • annotation
  • gene score
  • genome-wide association

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Genome-wide admixture and association analysis identifies African ancestry–specific risk loci of eosinophilic esophagitis in African Americans'. Together they form a unique fingerprint.

Cite this