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Aiming to define vitiligo subtypes, we discovered that age-of-onset is bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later onset (mean 34.0 years). In the early-onset subgroup we found novel association with MHC class II region indel rs145954018, and independent association with the principal MHC class II locus from previous GWAS, represented by rs9271597; greatest association was with rs145954018del-rs9271597A haplotype (<jats:italic>P<\/jats:italic>\u2009=\u20092.40\u2009\u00d7\u200910<jats:sup>\u221286<\/jats:sup>, OR\u2009=\u20098.10). Both rs145954018 and rs9271597 are located within lymphoid-specific enhancers, and the rs145954018del-rs9271597A haplotype is specifically associated with increased expression of <jats:italic>HLA-DQB1<\/jats:italic> mRNA and HLA-DQ protein by monocytes and dendritic cells. Thus, for vitiligo, MHC regulatory variation confers extreme risk, more important than <jats:italic>HLA<\/jats:italic> coding variation. MHC regulatory variation may represent a significant component of genetic risk for other autoimmune diseases.<\/jats:p>","DOI":"10.1038\/s41467-019-08337-4","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T11:32:59Z","timestamp":1548243179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression"],"prefix":"10.1038","volume":"10","author":[{"given":"Ying","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve H. 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