Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
Publication/Presentation Date
12-1-2013
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
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.
Volume
65
Issue
12
First Page
3239
Last Page
3247
ISSN
1529-0131
Published In/Presented At
Miller, F. W., Cooper, R. G., Vencovský, J., Rider, L. G., Danko, K., Wedderburn, L. R., Lundberg, I. E., Pachman, L. M., Reed, A. M., Ytterberg, S. R., Padyukov, L., Selva-O'Callaghan, A., Radstake, T. R., Isenberg, D. A., Chinoy, H., Ollier, W. E., O'Hanlon, T. P., Peng, B., Lee, A., Lamb, J. A., … Myositis Genetics Consortium (2013). Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis and rheumatism, 65(12), 3239–3247. https://doi.org/10.1002/art.38137
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
23983088
Department(s)
Department of Pediatrics
Document Type
Article