ArticleHuman molecular genetics2021
Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2023Pooled it
- Detailed stratified GWAS analysis for severe COVID-19 in four European populations.Human molecular genetics · 2022Pooled it
- Distinct predictive factors for acute severe ulcerative colitis in East Asian and Western populations.Inflammatory bowel diseases · 2026Observational
- Inflammatory and Immune Cytoprofiles of Active Ulcerative Colitis from Crohn's Disease-Insights from Multivariable Modeling.International journal of molecular sciences · 2026Article
- Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing.Journal of Crohn's & colitis · 2026Article
- T cell receptor clonotypes predict human leukocyte antigen allele carriage and antigen exposure history.Communications biology · 2026Article
- Multi-centered T cell repertoire profiling identifies alterations in the immune repertoire of individuals with inflammatory bowel disease across different disease stages.Genome medicine · 2026Article
- High throughput profiling of the B cell repertoire identifies systematic changes in the repertoire of individuals with Crohn's disease.Frontiers in immunology · 2026Article
- The Potential of β-Synuclein-Specific Regulatory T Cell Therapy as a Treatment for Progressive Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Elucidating biomarkers of carcinogenesis in ulcerative colitis: insight from Mendelian randomization and transcriptomics.Discover oncology · 2025Article
- Molecular Insight into the Role of HLA Genotypes in Immunogenicity and Secondary Refractoriness to Anti-TNF Therapy in IBD Patients.International journal of molecular sciences · 2025Review
- T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.Nature medicine · 2025Article
- Decoding the etiology of immune-mediated inflammatory diseases statistically.Frontiers in immunology · 2025Review
- Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options.International journal of molecular sciences · 2024Review
- Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes.Frontiers in immunology · 2024Review
- Regulatory SVA retrotransposons and classical HLA genotyped-transcripts associated with Parkinson's disease.Frontiers in immunology · 2024Article
- Mass Spectrometry-Based Immunopeptidomics of Peptides Presented on Human Leukocyte Antigen Proteins.Methods in molecular biology (Clifton, N.J.) · 2024Article
- HLA allele-calling using multi-ancestry whole-exome sequencing from the UK Biobank identifies 129 novel associations in 11 autoimmune diseases.Communications biology · 2023Article
- HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44Gastroenterology · 2023Article
- An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.Journal of Crohn's & colitis · 2023Article
Corrections and comments
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Authors and funding
53 authors at 20 institutions in 14 countries.
Funding
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
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