Linkage between HLA-B8 and HLA-DQ2.5 contributes to ancestry-dependent risk for celiac disease

Year: 2026

Type: article

Abstract: Limited genetic studies on celiac disease (CeD) are available for the Hispanic and black populations. We identified 3,481 individuals with CeD from the All of Us Research Program. Of these, 2,899 carried one of the four well-established risk haplotypes, including 262 of admixed American (89% Hispanic) and 108 of African (70% black) ancestry. An enrichment in the DQB1*02:01 allele was observed in CeD patients across all ancestries, with the strongest association in Europeans (32.3% vs. 11.6%), followed by Americans (18.5% vs. 8.1%) and Africans (15.7% vs. 8.1%). HLA-B8 conferred an additive risk for CeD independent of HLA-DQ2.5 across all three ancestries. The B8-DQ2.5 haplotype was significantly enriched in individuals with CeD but occurred at substantially lower frequencies in individuals with admixed American (3.2%) and African ancestry (1.2%) than in those with European ancestry (7.3%), accounting for ∼34% and 38% of the lower CeD prevalence, respectively. The frequency of the B8-DQ2.5 haplotype contributes to ancestry-dependent differences in CeD prevalence.

Source: Journal of Human Immunity

DOI: 10.70962/jhi.20260050

Authors: Xin Long, Hemanth Karnati, Wenjing Ying, Mary-Joe Touma, Ioana Smith, Suzanne K. Lewis, Chao Xing, Ezra Burstein, Peter H.R. Green, Michele J. Alkalay, Alexandre Bolze, Xiao-Fei Kong

Institutions: The University of Texas Southwestern Medical Center, Columbia University

Language: English

Topic: Celiac Disease Research and Management

Subfield: Gastroenterology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: U.S. Department of Health and Human Services, University of Texas Southwestern Medical Center, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

OpenAlex ID: W7211895360