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Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression

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Abstract
Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. 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 (P = 2.40 x 10(-86), OR = 8.10). Both rs145954018 and rs9271597 are located within lymphoid-specific enhancers, and the rs145954018del-rs9271597A haplotype is specifically associated with increased expression of HLA-DQB1 mRNA and HLA-DQ protein by monocytes and dendritic cells. Thus, for vitiligo, MHC regulatory variation confers extreme risk, more important than HLA coding variation. MHC regulatory variation may represent a significant component of genetic risk for other autoimmune diseases.
Keywords
GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, DNA ELEMENTS, DQ, PREVALENCE, DISEASES, RISK

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Chicago
Jin, Ying, Genevieve HL Roberts, Tracey M Ferrara, Songtao Ben, Nanja van Geel, Albert Wolkerstorfer, Khaled Ezzedine, et al. 2019. “Early-onset Autoimmune Vitiligo Associated with an Enhancer Variant Haplotype That Upregulates Class II HLA Expression.” Nature Communications 10.
APA
Jin, Y., Roberts, G. H., Ferrara, T. M., Ben, S., van Geel, N., Wolkerstorfer, A., Ezzedine, K., et al. (2019). Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression. NATURE COMMUNICATIONS, 10.
Vancouver
1.
Jin Y, Roberts GH, Ferrara TM, Ben S, van Geel N, Wolkerstorfer A, et al. Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression. NATURE COMMUNICATIONS. 2019;10.
MLA
Jin, Ying et al. “Early-onset Autoimmune Vitiligo Associated with an Enhancer Variant Haplotype That Upregulates Class II HLA Expression.” NATURE COMMUNICATIONS 10 (2019): n. pag. Print.
@article{8612827,
  abstract     = {Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. 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 (P = 2.40 x 10(-86), OR = 8.10). Both rs145954018 and rs9271597 are located within lymphoid-specific enhancers, and the rs145954018del-rs9271597A haplotype is specifically associated with increased expression of HLA-DQB1 mRNA and HLA-DQ protein by monocytes and dendritic cells. Thus, for vitiligo, MHC regulatory variation confers extreme risk, more important than HLA coding variation. MHC regulatory variation may represent a significant component of genetic risk for other autoimmune diseases.},
  articleno    = {391},
  author       = {Jin, Ying and Roberts, Genevieve HL and Ferrara, Tracey M and Ben, Songtao and van Geel, Nanja and Wolkerstorfer, Albert and Ezzedine, Khaled and Siebert, Janet and Neff, Charles P and Palmer, Brent E and Santorico, Stephanie A and Spritz, Richard A},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {GENOME-WIDE ASSOCIATION,SUSCEPTIBILITY LOCI,DNA ELEMENTS,DQ,PREVALENCE,DISEASES,RISK},
  language     = {eng},
  pages        = {10},
  title        = {Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression},
  url          = {http://dx.doi.org/10.1038/s41467-019-08337-4},
  volume       = {10},
  year         = {2019},
}

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