Genome-wide identification of m6A-associated single nucleotide polymorphisms in complex diseases of nervous system

N6-methyladenosine (m(6)A) is one of the most abundant chemical modifications on RNA and can affect the occurrence and development of diseases. Some studies have shown that the expressions of some m(6)A-related genes are significantly regulated by single nucleotide variants (SNV). However, the function of m(6)A-associated single nucleotide polymorphisms (m(6)A-SNP) remains unclear in multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Here, we identified the disease-associated m(6)A-SNPs by integrating genome-wide association study (GWAS) and m(6)A-SNPs from the RMVar database, and confirmed the relationship between these identified m(6)A-SNPs and their target genes in eQTL analysis and gene differential expression analysis. Finally, 26 genes corresponding to 20 m(6)A-SNPs with eQTL signals were identified and differentially expressed (P < 0.05) in MS, 15 genes corresponding to 12 m(6)A-SNPs (P < 1e-04) were differentially expressed in AD, and 27 PD-associated m(6)A-SNPs that regulated the expression of 31 genes were identified. There were 5 HLA genes with eQTL signals (HLA-DQB1, HLA-DRB1, HLA-DQA1, HLA-DQA2 and HLA-DQB1-AS1) to be detected in the three diseases. In summary, our study provided new insights into understanding the potential roles of these m(6)A-SNPs in disease pathogenesis as well as therapeutic target.

Automated summary

This study identified disease-associated m(6)A-SNPs and their target genes in multiple sclerosis, Alzheimer's disease, and Parkinson's disease. The results revealed that these SNPs can regulate the expression of multiple genes and there were specific HLA genes associated with these diseases.