长非编码RNA
单核苷酸多态性
自闭症谱系障碍
基因
生物
计算生物学
遗传学
自闭症
等位基因
生物信息学
核糖核酸
医学
基因型
精神科
作者
Haoxue Wang,Xvfang Wu,Yanlin Chen,Fang Hou,Kai Zhu,Q. Jiang,Ping Xiao,Quan Zhang,Zhou Xiang,Yixi Fan,Xinyan Xie,Li Li,Ranran Song
标识
DOI:10.1016/j.ajp.2022.103357
摘要
Rising evidence has indicated that long non-coding RNA (lncRNA) may play an essential role in the development of autism spectrum disorder (ASD). However, identifying the lncRNAs associated with ASD and the risk loci on them remains a major challenge. This study aims to identify potential causative variants and explore the related mechanisms.By leveraging differential expression analysis, WGCNA analysis and cis-expression quantitative analysis, our study mined functional SNPs with the regulated long non-coding RNA genes in brain tissues. We recruited 611 ASD children and 645 healthy children in the case-control study.Total 68 different expressed lncRNAs were validated by calculating the brain tissue-specific expression using RNA-seq data. By the WGCNA method, 9 functional lncRNAs classified as e-lncRNA were found to interact with 976 ASD risk genes. Furthermore, we mined functional SNPs regulated long non-coding RNAs in brain tissues. We analyzed the association between candidate SNPs and ASD risks in Chinese children, which showed BDNF-AS rs1565228 allele G to C reduced the risk of ASD (OR = 0.81, 95%CI: 0.66-0.98). Further bioinformatics analysis showed that the variant rs1565228 C>G with the low binding affinity of transcription factor SRF caused the decreased expression of lncRNA BDNF-AS. Our study revealed that rs2295412 in the non-coding sequence of the lncRNA gene region was significantly associated with the risk of ASD.These findings suggested that the SNPs in the non-coding region of lncRNA may play important roles in the genetic susceptibility of ASD, which may facilitate the early screening of ASD.
科研通智能强力驱动
Strongly Powered by AbleSci AI