Genome‐Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders1. Issue 12 (December 2013)

• Record Type: Journal Article
• Authors: Miller, Frederick W.; Cooper, Robert G.; Vencovský, Jiří; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva‐O'Callaghan, Albert; Radstake, Timothy R. D. J.; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O'Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.; with the Myositis Genetics Consortium
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 12(2013:Dec.)
• Page Start: 3239
• Page End: 3247
• Publication Date: 2013-12
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.38137
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38137-sec-0001" sec-type="section"> <title>Objective</title> <p>To identify new genetic associations with juvenile and adult dermatomyositis (DM).</p> </sec> <sec id="art38137-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="art38137-sec-0003" sec-type="section"> <title>Results</title> <p>Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (<italic>P</italic> < 5 × 10<sup>–8</sup>) 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 (<italic>PLCL1</italic>; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (<italic>BLK</italic>; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (<italic>CCL21</italic>; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.</p> </sec> <sec id="art38137-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>