Journal article
Genome-Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders
Arthritis and rheumatism, Vol.65(12), pp.3239-3247
12/2013
DOI: 10.1002/art.38137
PMCID: PMC3934004
PMID: 23983088
Abstract
Objective
To identify new genetic associations with juvenile and adult dermatomyositis (DM).
Methods
We performed a genomeâ€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 singleâ€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 GWASâ€level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 nonâ€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 (Câ€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 nonâ€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.
Details
- Title: Subtitle
- Genome-Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders
- Creators
- Wei Chen - M. D. Anderson Cancer CenterFrederick W Miller - National Institute of Environmental Health Sciences, NIHRobert G Cooper - Salford Royal National Health Service Foundation TrustJiří Vencovský - Institute of RheumatologyLisa G Rider - National Institute of Environmental Health Sciences, NIHKatalin Danko - University of DebrecenLucy R Wedderburn - University College LondonIngrid E Lundberg - Karolinska InstitutetLauren M Pachman - Children's Hospital of Chicago and Northwestern University Feinberg School of MedicineAnn M Reed - Mayo ClinicSteven R Ytterberg - Mayo ClinicLeonid Padyukov - Karolinska InstitutetAlbert Selva‐O'Callaghan - Vall d'Hebron General HospitalTimothy R. D. J Radstake - Nijmegen Center for Molecular Life SciencesDavid A Isenberg - University College LondonHector Chinoy - University of ManchesterWilliam E. R Ollier - University of ManchesterTerrance P O'Hanlon - National Institute of Environmental Health Sciences, NIHBo Peng - M. D. Anderson Cancer CenterAnnette Lee - North Shore LIJ–Health System and Feinstein Institute for Medical ResearchJanine A Lamb - University of ManchesterChristopher I Amos - M. D. Anderson Cancer CenterPeter K Gregersen - North Shore LIJ–Health System and Feinstein Institute for Medical ResearchMyositis Genetics Consortium
- Contributors
- Scott A Vogelgesang (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Arthritis and rheumatism, Vol.65(12), pp.3239-3247
- DOI
- 10.1002/art.38137
- PMID
- 23983088
- PMCID
- PMC3934004
- NLM abbreviation
- Arthritis Rheum
- ISSN
- 0004-3591
- eISSN
- 1529-0131
- Publisher
- Wley
- Number of pages
- 9
- Grant note
- NIH (Intramural Program, National Institute of Environmental Health Sciences) (Z01‐ES‐101074) Wellcome Trust Arthritis Research UK (18474) Cure JM Foundation Henry Smith Charity (UK) UK Myositis Support Group Ministry of Health, Czech Republic (00023728) European Union Sixth Framework Programme (project AutoCure) (LSHB CT‐2006‐018661) European Science Foundation Action Medical Research (UK) Swedish Research Council
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Immunology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984094492002771
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