Genome-wide identification of cell type-specific susceptibility genes for Juvenile dermatomyositis through the analysis of N-methyladenosine-associated SNPs.

Genome-wide association studies (GWASs) have pinpointed genetic loci associated with juvenile dermatomyositis (JDM). Functional genes within the GWAS loci may be cell type-specific, but their identity remains largely unknown. N-methyladenosine (mA) plays a pivotal role in regulating various cellular processes and is linked to autoimmune diseases. This study aimed to underscore the potential functional genes within the GWAS loci through the analysis of mA-associated SNPs (mA-SNPs), specifically within relevant cell types. JDM-associated mA-SNPs were identified from the GWAS summary dataset. The correlation between mA-SNPs and gene expression was assessed through bulk tissue and single-cell eQTL analyses. To further investigate the relationship between gene expression and JDM, Mendelian randomization analysis was employed. Additionally, differential expression analyses were conducted on bulk tissues, as well as single-cell transcriptomic data comprising 6 JDM patients and 11 juvenile controls (99,396 cells). Seven mA-SNPs associated with JDM were identified. Bulk tissue analysis revealed differential expression of , , , , , , , , , , , and influenced by mA-SNPs, all showing associations with JDM in both differential expression and Mendelian randomization analyses. In single-cell analysis, the six mA-SNPs within the HLA locus acted as cell-type-specific eQTLs, correlating with the expression of , , , , , and in myeloid, T or B cells. Notably, these genes displayed abnormal expression in T, B, and myeloid cells of JDM patients. The present study identified mA-SNPs within JDM susceptibility genes, shedding light on the intricate interplay between mA-SNPs, gene expression, and JDM.