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

Neurosci Lett. 2023 Nov 20:817:137513. doi: 10.1016/j.neulet.2023.137513. Epub 2023 Oct 10.


N6-methyladenosine (m6A) 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 m6A-related genes are significantly regulated by single nucleotide variants (SNV). However, the function of m6A-associated single nucleotide polymorphisms (m6A-SNP) remains unclear in multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Here, we identified the disease-associated m6A-SNPs by integrating genome-wide association study (GWAS) and m6A-SNPs from the RMVar database, and confirmed the relationship between these identified m6A-SNPs and their target genes in eQTL analysis and gene differential expression analysis. Finally, 26 genes corresponding to 20 m6A-SNPs with eQTL signals were identified and differentially expressed (P < 0.05) in MS, 15 genes corresponding to 12 m6A-SNPs (P < 1e-04) were differentially expressed in AD, and 27 PD-associated m6A-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 m6A-SNPs in disease pathogenesis as well as therapeutic target.

Keywords: Alzheimer's disease; Genome-wide association study (GWAS); Multiple sclerosis; N6-methyladenosine (m(6)A); Parkinson's disease; Single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Multiple Sclerosis* / pathology
  • Parkinson Disease* / genetics
  • Polymorphism, Single Nucleotide