title: Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland.
authors: Frederick W
authors: FW
authors: Miller
authors: Robert G
authors: RG
authors: Cooper
authors: Jiří
authors: J
authors: Vencovský
authors: Lisa G
authors: LG
authors: Rider
authors: Katalin
authors: K
authors: Danko
authors: Lucy R
authors: LR
authors: Wedderburn
authors: Ingrid E
authors: IE
authors: Lundberg
authors: Lauren M
authors: LM
authors: Pachman
authors: Ann M
authors: AM
authors: Reed
authors: Steven R
authors: SR
authors: Ytterberg
authors: Leonid
authors: L
authors: Padyukov
authors: Albert
authors: A
authors: Selva-O'Callaghan
authors: Timothy R D J
authors: TR
authors: Radstake
authors: David A
authors: DA
authors: Isenberg
authors: Hector
authors: H
authors: Chinoy
authors: William E R
authors: WE
authors: Ollier
authors: Terrance P
authors: TP
authors: O'Hanlon
authors: Bo
authors: B
authors: Peng
authors: Annette
authors: A
authors: Lee
authors: Janine A
authors: JA
authors: Lamb
authors: Wei
authors: W
authors: Chen
authors: Christopher I
authors: CI
authors: Amos
authors: Peter K
authors: PK
authors: Gregersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D003882:Dermatomyositis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
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