Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Genome-Wide Association Study of Dermatomyositis Reveals Shared Genetic Risk Factors with Other Autoimmune Diseases.

Miller1,  Frederick W., Cooper2,  Robert G., Vencovsky3,  Jiri, Rider4,  Lisa G., Danko5,  Katalin, Wedderburn6,  Lucy R., Lundberg7,  Ingrid E.

NIH/NIEHS NIH Bldg 10 4–2330, Bethesda, MD
Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
Hospital Universitari General Vall d'Hebron, Barcelona, Spain
Geert Groote Plein 8, Nymegen, Netherlands
University College London, London WC1E 6JF, United Kingdom
Manchester, United Kingdom
Univ of Manchester Med School, Manchester, United Kingdom
NIH, Bethesda, MD
Houston, TX
Feinstein Institute Med Rsch, Manhasset, NY
Feinstein Institute Medical Reschearch, Manhasset, NY
Hope Hospital, Salford, United Kingdom
Institute of Rheumatology, Prague 2, Czech Republic
NIEHS NIH, Bethesda, MD
University of Debrecen, Debrecen, Hungary, Debrecan, Hungary
University College London (UCL), United Kingdom
Karolinska Institutet, Stockholm, Sweden
Northwestern University Feinberg School of Medicine, Chicago, IL
Mayo Clinic, Rochester, MN


Genetic risk factors for adult dermatomyositis (DM) and juvenile DM outside of the major histocompatibility complex (MHC) have been difficult to identify, although family studies have suggested that DM shares genetic risk factors with other autoimmune diseases.


We performed a genome-wide association study (GWAS) on adult DM and juvenile DM subjects of European ancestry meeting probable or definite Bohan and Peter criteria using the Illumina platform. DM cases (n=1178: 705 with adult DM and 473 with juvenile DM) were compared to geographically- and race-matched controls (n=4724). Ingenuity Systems Pathway Analyses were performed based on the genes identified by GWAS.


As expected, we observed a strong signal in the MHC locus across the class II region (maximum p=2.79×10-29) but no other locus reached genome-wide significance in this dataset. To assess for possible shared genes with other autoimmune diseases, however, we examined the association signals in 140 non-MHC loci that have been associated with autoimmune diseases. Strikingly, seven SNPs from six genes had p values <= 0.01, thus substantially exceeding expectation. These included: B lymphocyte kinase (BLK: rs2736340, p=6.53×10-5); chemokine (C-C motif) ligand 21 (CCL21: rs2492358, p=2.10×10-4; and rs951005, p=3.17×10-5); protein tyrosine phosphatase non-receptor type 2 (PTPN2: rs1893217, p=0.0029); signal transducer and activator of transcription 4 (STAT4: rs7574865, p=0.0050); interleukin 2 receptor alpha (IL2RA: rs7072793, p=0.0073); and a gene encoding a 153–amino acid protein with four putative transmembrane domains (ORMDL3: rs2290400, p=0.0010). Based on the associated genes from the entire GWAS, canonical pathways that seemed particularly important in DM were those relating to antigen presentation (p=9.49×10-23), cytotoxic T cell-mediated apoptosis of target cells (p=1.44×10-17), allograft rejection signaling (p=1.44×10-17), the OX40 (CD134) signaling pathway (p=5.9×10-17) and autoimmune thyroid disease signaling (p=5.0×10-13).


Our findings indicate that DM shares many genetic features and canonical pathways with other autoimmune diseases. This first identification of these common autoimmune disease genetic predispositions that promote the development of DM suggests potential novel therapeutic approaches for this disorder.

To cite this abstract, please use the following information:
Miller, Frederick W., Cooper, Robert G., Vencovsky, Jiri, Rider, Lisa G., Danko, Katalin, Wedderburn, Lucy R., et al; Genome-Wide Association Study of Dermatomyositis Reveals Shared Genetic Risk Factors with Other Autoimmune Diseases. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1678

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