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Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

Publication ,  Journal Article
Miller, FW; Chen, W; O'Hanlon, TP; Cooper, RG; Vencovsky, J; Rider, LG; Danko, K; Wedderburn, LR; Lundberg, IE; Pachman, LM; Reed, AM; Peng, B ...
Published in: Genes Immun
October 2015

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P<5×10(-8)) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

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Published In

Genes Immun

DOI

EISSN

1476-5470

Publication Date

October 2015

Volume

16

Issue

7

Start / End Page

470 / 480

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Polymyositis
  • Polymorphism, Single Nucleotide
  • Myositis
  • Middle Aged
  • Male
  • Immunology
  • Humans
  • Haplotypes
 

Citation

APA
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ICMJE
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Miller, F. W., Chen, W., O’Hanlon, T. P., Cooper, R. G., Vencovsky, J., Rider, L. G., … Myositis Genetics Consortium, . (2015). Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes. Genes Immun, 16(7), 470–480. https://doi.org/10.1038/gene.2015.28
Miller, F. W., W. Chen, T. P. O’Hanlon, R. G. Cooper, J. Vencovsky, L. G. Rider, K. Danko, et al. “Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.Genes Immun 16, no. 7 (October 2015): 470–80. https://doi.org/10.1038/gene.2015.28.
Miller FW, Chen W, O’Hanlon TP, Cooper RG, Vencovsky J, Rider LG, et al. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes. Genes Immun. 2015 Oct;16(7):470–80.
Miller, F. W., et al. “Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.Genes Immun, vol. 16, no. 7, Oct. 2015, pp. 470–80. Pubmed, doi:10.1038/gene.2015.28.
Miller FW, Chen W, O’Hanlon TP, Cooper RG, Vencovsky J, Rider LG, Danko K, Wedderburn LR, Lundberg IE, Pachman LM, Reed AM, Ytterberg SR, Padyukov L, Selva-O’Callaghan A, Radstake TR, Isenberg DA, Chinoy H, Ollier WER, Scheet P, Peng B, Lee A, Byun J, Lamb JA, Gregersen PK, Amos CI, Myositis Genetics Consortium. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes. Genes Immun. 2015 Oct;16(7):470–480.

Published In

Genes Immun

DOI

EISSN

1476-5470

Publication Date

October 2015

Volume

16

Issue

7

Start / End Page

470 / 480

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Polymyositis
  • Polymorphism, Single Nucleotide
  • Myositis
  • Middle Aged
  • Male
  • Immunology
  • Humans
  • Haplotypes