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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. 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.

SUBMITTER: Miller FW

PROVIDER: S-EPMC3934004 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Miller Frederick W FW Cooper Robert G RG Vencovský Jiří J Rider Lisa G LG Danko Katalin K Wedderburn Lucy R LR Lundberg Ingrid E IE Pachman Lauren M LM Reed Ann M AM Ytterberg Steven R SR Padyukov Leonid L Selva-O'Callaghan Albert A Radstake Timothy R D J TR Isenberg David A DA Chinoy Hector H Ollier William E R WE O'Hanlon Terrance P TP Peng Bo B Lee Annette A Lamb Janine A JA Chen Wei W Amos Christopher I CI Gregersen Peter K PK

Arthritis and rheumatism 20131201 12

<h4>Objective</h4>To identify new genetic associations with juvenile and adult dermatomyositis (DM).<h4>Methods</h4>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, predisp ...[more]

PMID: 23983088

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

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

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