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

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

doi:10.1016/j.neulet.2023.137513

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.

Authors

Fei Guo¹, Jingxuan Kang¹, Jing Xu¹, Siyu Wei², Junxian Tao¹, Yu Dong¹, Yingnan Ma¹, Hongsheng Tian², Xuying Guo², Shuo Bi², Chen Zhang², Hongchao Lv², Zhenwei Shang², Yongshuai Jiang³, Mingming Zhang⁴

Affiliations

¹ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; The EWAS Project, China.
² College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
³ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; The EWAS Project, China. Electronic address: jiangyongshuai@hrbmu.edu.cn.
⁴ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; The EWAS Project, China. Electronic address: zhangmingming@hrbmu.edu.cn.

PMID: 37827449
DOI: 10.1016/j.neulet.2023.137513

Abstract

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