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Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data.

Abstract

The pathogenesis of multiple sclerosis (MS) is significantly regulated by long noncoding RNAs (lncRNAs), the expression of which is substantially influenced by a number of MS-associated risk single nucleotide polymorphisms (SNPs). It is thus hypothesized that the dysregulation of lncRNA induced by genomic variants may be one of the key molecular mechanisms for the pathology of MS. However, due to the lack of sufficient data on lncRNA expression and SNP genotypes of the same MS patients, such molecular mechanisms underlying the pathology of MS remain elusive. In this study, a bioinformatics strategy was applied to obtain lncRNA expression and SNP genotype data simultaneously from 142 samples (51 MS patients and 91 controls) based on RNA-seq data, and an expression quantitative trait loci (eQTL) analysis was conducted. In total, 2383 differentially expressed lncRNAs were identified as specifically expressing in brain-related tissues, and 517 of them were affected by SNPs. Then, the functional characterization, secondary structure changes and tissue and disease specificity of the cis-eQTL SNPs and lncRNA were assessed. The cis-eQTL SNPs were substantially and specifically enriched in neurological disease and intergenic region, and the secondary structure was altered in 17.6% of all lncRNAs in MS. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate how the influence of SNPs on lncRNAs contributed to the pathogenesis of MS. As a result, the regulation of lncRNAs by SNPs was found to mainly influence the antigen processing/presentation and mitogen-activated protein kinases (MAPK) signaling pathway in MS. These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS.

Authors+Show Affiliations

Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. School of Pharmaceutical Sciences and Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, China.School of Pharmaceutical Sciences and Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, China.Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, School of Medicine, Hangzhou Normal University, Hangzhou, China.Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. School of Pharmaceutical Sciences and Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31323688

Citation

Han, Zhijie, et al. "Genome-wide Identification and Analysis of the eQTL lncRNAs in Multiple Sclerosis Based On RNA-seq Data." Briefings in Bioinformatics, 2019.
Han Z, Xue W, Tao L, et al. Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data. Brief Bioinformatics. 2019.
Han, Z., Xue, W., Tao, L., Lou, Y., Qiu, Y., & Zhu, F. (2019). Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data. Briefings in Bioinformatics, doi:10.1093/bib/bbz036.
Han Z, et al. Genome-wide Identification and Analysis of the eQTL lncRNAs in Multiple Sclerosis Based On RNA-seq Data. Brief Bioinformatics. 2019 Apr 24; PubMed PMID: 31323688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data. AU - Han,Zhijie, AU - Xue,Weiwei, AU - Tao,Lin, AU - Lou,Yan, AU - Qiu,Yunqing, AU - Zhu,Feng, Y1 - 2019/04/24/ PY - 2018/11/15/received PY - 2019/03/05/revised PY - 2019/03/06/accepted PY - 2019/7/20/entrez PY - 2019/7/20/pubmed PY - 2019/7/20/medline KW - RNA-seq KW - expression quantitative trait loci KW - function analysis KW - long non-coding RNAs KW - multiple sclerosis JF - Briefings in bioinformatics JO - Brief. Bioinformatics N2 - The pathogenesis of multiple sclerosis (MS) is significantly regulated by long noncoding RNAs (lncRNAs), the expression of which is substantially influenced by a number of MS-associated risk single nucleotide polymorphisms (SNPs). It is thus hypothesized that the dysregulation of lncRNA induced by genomic variants may be one of the key molecular mechanisms for the pathology of MS. However, due to the lack of sufficient data on lncRNA expression and SNP genotypes of the same MS patients, such molecular mechanisms underlying the pathology of MS remain elusive. In this study, a bioinformatics strategy was applied to obtain lncRNA expression and SNP genotype data simultaneously from 142 samples (51 MS patients and 91 controls) based on RNA-seq data, and an expression quantitative trait loci (eQTL) analysis was conducted. In total, 2383 differentially expressed lncRNAs were identified as specifically expressing in brain-related tissues, and 517 of them were affected by SNPs. Then, the functional characterization, secondary structure changes and tissue and disease specificity of the cis-eQTL SNPs and lncRNA were assessed. The cis-eQTL SNPs were substantially and specifically enriched in neurological disease and intergenic region, and the secondary structure was altered in 17.6% of all lncRNAs in MS. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate how the influence of SNPs on lncRNAs contributed to the pathogenesis of MS. As a result, the regulation of lncRNAs by SNPs was found to mainly influence the antigen processing/presentation and mitogen-activated protein kinases (MAPK) signaling pathway in MS. These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS. SN - 1477-4054 UR - https://www.unboundmedicine.com/medline/citation/31323688/Genome-wide_identification_and_analysis_of_the_eQTL_lncRNAs_in_multiple_sclerosis_based_on_RNA-seq_data L2 - https://academic.oup.com/bib/article-lookup/doi/10.1093/bib/bbz036 DB - PRIME DP - Unbound Medicine ER -