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Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.

Publication ,  Journal Article
Miller, FW; Cooper, RG; Vencovský, J; Rider, LG; Danko, K; Wedderburn, LR; Lundberg, IE; Pachman, LM; Reed, AM; Ytterberg, SR; Padyukov, L ...
Published in: Arthritis Rheum
December 2013

OBJECTIVE: To identify new genetic associations with juvenile and adult dermatomyositis (DM). METHODS: We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single-nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. RESULTS: Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5 × 10(-8)) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C-like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C-C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM. CONCLUSION: Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.

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Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

December 2013

Volume

65

Issue

12

Start / End Page

3239 / 3247

Location

United States

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Dermatomyositis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Miller, F. W., Cooper, R. G., Vencovský, J., Rider, L. G., Danko, K., Wedderburn, L. R., … Myositis Genetics Consortium, . (2013). Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum, 65(12), 3239–3247. https://doi.org/10.1002/art.38137
Miller, Frederick W., Robert G. Cooper, Jiří Vencovský, Lisa G. Rider, Katalin Danko, Lucy R. Wedderburn, Ingrid E. Lundberg, et al. “Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.Arthritis Rheum 65, no. 12 (December 2013): 3239–47. https://doi.org/10.1002/art.38137.
Miller FW, Cooper RG, Vencovský J, Rider LG, Danko K, Wedderburn LR, et al. Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum. 2013 Dec;65(12):3239–47.
Miller, Frederick W., et al. “Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.Arthritis Rheum, vol. 65, no. 12, Dec. 2013, pp. 3239–47. Pubmed, doi:10.1002/art.38137.
Miller FW, Cooper RG, Vencovský J, Rider LG, Danko K, Wedderburn LR, Lundberg IE, Pachman LM, Reed AM, Ytterberg SR, Padyukov L, Selva-O’Callaghan A, Radstake TRDJ, Isenberg DA, Chinoy H, Ollier WER, O’Hanlon TP, Peng B, Lee A, Lamb JA, Chen W, Amos CI, Gregersen PK, Myositis Genetics Consortium. Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum. 2013 Dec;65(12):3239–3247.
Journal cover image

Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

December 2013

Volume

65

Issue

12

Start / End Page

3239 / 3247

Location

United States

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Dermatomyositis