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

单核苷酸多态性 表达数量性状基因座 生物 遗传学 全基因组关联研究 SNP公司 基因 遗传关联 基因型
作者
Fei Guo,Jingxuan Kang,Jing Xu,Siyu Wei,Junxian Tao,Yu Dong,Yingnan Ma,Hongsheng Tian,Xuying Guo,Shuo Bi,Chen Zhang,Hongchao Lv,Zhenwei Shang,Yongshuai Jiang,Mingming Zhang
出处
期刊:Neuroscience Letters [Elsevier]
卷期号:817: 137513-137513 被引量:2
标识
DOI:10.1016/j.neulet.2023.137513
摘要

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.
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