ArticleHuman molecular genetics2014
Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 3 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 3 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.Journal of the American Society of Nephrology : JASN · 2020Pooled it
- Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.Communications biology · 2020Pooled it
- Genetics of idiopathic inflammatory myopathies: insights into disease pathogenesis.Current opinion in rheumatology · 2019Pooled it
- Review
- Article
- Epigenetic alterations in rheumatoid arthritis: multilayer mechanisms and translational opportunities.Frontiers in immunology · 2026Review
- Functional dissection of noncoding variants associated with rheumatoid arthritis.Annals of the rheumatic diseases · 2025Article
- Article
- HLA-B*58 and HLA-C*2 Alleles Are Associated with the Occurrence of Rheumatoid Arthritis Among Omanis.Journal of clinical medicine · 2025Article
- Article
- The Role of Vimentin Peptide Citrullination in the Structure and Dynamics of HLA-DRB1 Rheumatoid Arthritis Risk-Associated Alleles.International journal of molecular sciences · 2024Article
- Identification of epistatic SNP combinations in rheumatoid arthritis using LAMPLINK and Japanese cohorts.Journal of human genetics · 2024Article
- Efficient HLA imputation from sequential SNPs data by transformer.Journal of human genetics · 2024Review
- Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis.Scientific reports · 2024Article
- Fibroblasts in rheumatoid arthritis: novel roles in joint inflammation and beyond.Frontiers in medicine · 2024Review
- Immunomodulatory nano-preparations for rheumatoid arthritis.Drug delivery · 2023Review
- Contribution ofInternational journal of molecular sciences · 2023Article
- Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis.Cell reports. Medicine · 2023Article
- A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations.The journal of allergy and clinical immunology. Global · 2023Article
- Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 10 countries.
Funding
Abstract
Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope (Pomnibus = 6.9 × 10(-135)). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ≅ Gly > Ser)--but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional Pomnibus = 2.2 × 10(-33)) and 74 (conditional Pomnibus = 1.1 × 10(-8)). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 × 10(-6)) and HLA-DPβ1 (Phe9, conditional P = 3.0 × 10(-5)) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.