Genome-wide identification of m6A-associated single-nucleotide polymorphisms in Parkinson' s disease
Genome-wide identification of m6A-associated single-nucleotide polymorphisms in Parkinson' s disease
复制标题
帕金森病 m(6)A 相关单核苷酸多态性的全基因组鉴定。
DOI：
10.1016/j.neulet.2020.135315
复制
发表时间：
2020-10-15
影响因子：
2.5
通讯作者：
Xiao, Yousheng
中科院分区：
文献类型：
--
作者：
Qiu, Xiaohui;He, Honghu;Xiao, Yousheng
N6-甲基腺苷(m(6)A)相关的单核苷酸多态(SNPs)在多种神经系统疾病中起重要作用。然而，关于m(6)A修饰与帕金森氏病(PD)之间的关系却知之甚少。我们研究了来自大规模全基因组关联研究的帕金森病患者中m(6)A-SNPs的潜在功能变异。通过表达数量性状基因座(EQTL)分析和差异基因表达分析对候选的m(6)A-SNPs进行分析。我们确定了12个与帕金森病风险显著相关的A-SNP。此外，eQTL和表达分析发现其中5个m6ASNP(GAK的rs75072999，ALKBH5的rs4924839和rs8071834，以及C6orf10的rs1033500)与PD的基因表达变化相关。我们的结果提示m(6)A-SNPs可能在帕金森病的发病风险中起作用。需要进一步的研究来证实这些与PD相关的m(6)A-SNPs，并阐明其机制。
N6-methyladenosine (m(6)A)-associated single nucleotide polymorphisms (SNPs) play a vital role in several neurological diseases. However, little is known about the relationship between m(6)A modification and Parkin-son's disease (PD). We investigated potential functional variants of m(6)A-SNPs from large-scale genome-wide association studies (GWAS) in PD patients. The candidate m(6)A-SNPs were further assessed by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We identified 12 m(6)A-SNPs that were significantly associated with PD risk. Further, eQTL and expression analyses identified five of these m6ASNPs (rs75072999 of GAK, rs1378602, rs4924839 and rs8071834 of ALKBH5, and rs1033500 of C6orf10) that were associated with altered gene expression in PD. Our results suggest that m(6)A-SNPs could play a role in PD risk. Future studies are needed to confirm these PD-associated m(6)A-SNPs and elucidate their mechanisms.