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With 354 ACPA\u2010positive RA patients and 335 normal controls selected from a case\u2013control study based on Swedish population, we conducted the first RA epigenome\u2010wide meplotype association study using our software EWAS2.0, mainly including (i) converted the \u03b2 value to methylation genotype (menotype) data, (ii) identified methylation disequilibrium (MD) block, (iii) calculated frequent of each meplotypes in MD block and performed case\u2013control association test and (iv) screened for RA\u2010risk meplotypes by odd ratio (OR) and <jats:italic>p<\/jats:italic>\u2010values. Ultimately, 545 meplotypes on 334 MD blocks were identified significantly associated with RA (<jats:italic>p<\/jats:italic>\u2010value\u00a0&lt;\u00a0.05). These meplotypes were mapped to 329 candidate genes related to RA. Subsequently, combined with gene optimization, eight RA\u2010risk meplotypes were identified on three risk genes: HLA\u2010DRB1, HLA\u2010DRB5 and HLA\u2010DQB1. Our results reported the relationship between DNA methylation pattern on HLA\u2010DQB1 and the risk of RA for the first time, demonstrating the co\u2010demethylation of \u2018cg22984282\u2019 and \u2018cg13423887\u2019 on HLA\u2010DQB1 gene (meplotype UU, <jats:italic>p<\/jats:italic>\u2010value\u00a0=\u00a02.90E\u00a0\u2212\u00a06, OR\u00a0=\u00a01.68, 95% CI\u00a0=\u00a0[1.35, 2.10]) may increase the risk of RA. Our results demonstrates the potential of methylation haplotype analysis to identify RA\u2010related genes from a new perspective and its applicability to the study of other disease.<\/jats:p>","DOI":"10.1111\/iji.12637","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T12:19:08Z","timestamp":1694261948000},"page":"291-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Epigenome\u2010wide methylation haplotype association analysis identified HLA\u2010DRB1, HLA\u2010DRB5 and HLA\u2010DQB1 as risk factors for rheumatoid arthritis"],"prefix":"10.1111","volume":"50","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of 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