Linkage between HLA-B8 and HLA-DQ2.5 contributes to ancestry-dependent risk for celiac disease
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Using data from the All of Us Research Program, Xin Long et al. found that HLA-DQ2.5, the major genetic risk for celiac disease, is present across diverse populations. However, its linkage with HLA-B8 varies by genetic ancestry and contributes to differences in disease prevalence. teaser 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 theallele 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. Graphical Abstract A diagram illustrating the AH8.1 haplotype, genetic ancestries, and celiac disease prevalence. A chromosome with labeled gene
Abstract
Using data from the All of Us Research Program, Xin Long et al. found that HLA-DQ2.5, the major genetic risk for celiac disease, is present across diverse populations. However, its linkage with HLA-B8 varies by genetic ancestry and contributes to differences in disease prevalence. teaser 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 theallele 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. Graphical Abstract A diagram illustrating the AH8.1 haplotype, genetic ancestries, and celiac disease prevalence. A chromosome with labeled genes includes HLA-A, HLA-C, HLA-B, TNF, DRB1, DQA1, DQB1, DPA1, and DPB1. A scatter plot representing genetic ancestries. The prevalence of celiac disease is also shown, highlighting the HLA-DQ2.5 and B8-DQ2.5 haplotype. The diagram compares the prevalence of celiac disease among European, Admixed American, and African populations, showing percentages for each group. http://www.w3.org/1999/xlink float portrait jhi_20260050_ga.webp float GA portrait graphical