Causal relationship between dermatomyositis and autoimmune d isorders: a Mendelian randomization study

Background Various autoimmune disorders have been linked to dermatomyositis (DM) based on findings from epidemiological studies. The objective of this study is to examine the causal association between autoimmune disorders and DM utilizing the methodology of Mendelian randomization (MR). Methods We employed summary statistics from the largest European genome-wide association studies (GWAS) on autoimmune disorders to assess the genetically predicted effects on DM risk in a two-sample MR framework. Single nucleotide polymorphisms (SNPs) strongly associated with 10 immune-related traits were extracted from these GWAS datasets and their effects were examined in a European DM GWAS cohort (201 cases and 172834 controls). In order to address potential bias arising from the intricate linkage disequilibrium structure observed in the human leukocyte antigen region, the analysis excluded SNPs within this specific genomic region. Subsequently, a multivariate Mendelian analysis was conducted to investigate the association between one autoimmune disease and DM. Results After applying the Bonferroni correction to account for multiple testing, our MR analyses revealed a potential heightened risk of DM associated with type 1 diabetes (T1D), one of the autoimmune diseases under investigation. We further conducted a Mendelian analysis focusing on T1D and the occurrence of DM, incorporating type 2 diabetes, viral infection, sunburns and smoking status. Our findings revealed that T1D independently increased the risk of DM, regardless of smoking and viral infection, which were previously identified as DM risk factors. Conclusion Our MR study provides evidence supporting a relationship between susceptibility to T1D and increased DM risk in the European population.