Investigation of idiopathic inflammatory myopathy for shared genetic risk factors with other autoimmune diseases: results from the European Myositis Network

Abstract

BackgroundIdiopathic inflammatory myopathies (IIM) are a group of autoimmune disorders characterised by inflammation of muscles. They may present as a primary disorder or may overlap with other diseases such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. The cause of IIM is largely unknown, but is thought to include a combination of both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified many genetic variants associated with autoimmune disorders, several of which are common to multiple disorders. We tested the hypothesis that genetic risk factors associated with other autoimmune disorders also predispose to IIM. MethodsSingle-nucleotide polymorphisms (SNPs) significantly associated with systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, coeliac disease, inflammatory bowel disease, psoriasis, type 1 diabetes, multiple sclerosis, and systemic sclerosis were identified from published GWAS in white populations. 233 unique SNPs were identified (p<5 × 10−8), of which 99 had not been captured through our international myositis genetic collaboration GWAS. These SNPs were genotyped in a sample of 1043 European white individuals with adult or juvenile dermatomyositis or polymyositis who were compared with race-matched controls. Analysis was carried out with PLINK, followed by fixed-effects meta-analysis. Findings1001 individuals and 83 SNPs passed quality control filtering criteria and were genotyped. Two SNPs within the HLA region were significantly associated with IIM (rs2040406 near HLA-DQA1, p=2·23 × 10 −38 and rs615672 near HLA-DRB1, p=6·07 × 10−13). Two SNPs outside the HLA region achieved Bonferroni corrected significance levels (type 1 diabetes rs11171739, p=3·01 × 10−7 and multiple sclerosis rs3135388, p= 9·71 × 10−7). SNPs associated with the genes FAM107A, TNFAIP3, and BLK, previously linked with rheumatoid arthritis and systemic lupus erythematosus, were also associated with IIM. InterpretationThe association of HLA SNPs confirms the autoimmune nature of IIM. The association of SNPs previously associated with type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis suggests that IIM may share genetic risk factors with other autoimmune disorders. FundingUK Medical Research Council and UK Myositis Support Group.