title: Integrative multi-omics analysis revealed SNP-lncRNA-mRNA (SLM) networks in human peripheral blood mononuclear cells.
abstract: Long non-coding RNAs (lncRNAs) serve as important controller of cellular functions via regulating RNA transcription, degradation and translation. However, what are the regulation patterns of lncRNAs on downstream mRNA and how the upstream genetic variants regulate lncRNAs are largely unknown. We first performed a comprehensive expression quantitative trait locus (eQTL) analysis (MatrixeQTL package, R) using genome-wide lncRNA expression and SNP genotype data from human peripheral blood mononuclear cells (PBMCs) of 43 unrelated individuals. Subsequently, multi-omics integrative network analysis was applied to construct SNP-lncRNA-mRNA (SLM) interaction networks. The causal inference test (CIT) was used to identify lncRNA-mediated (epi-) genetic regulation on mRNA expressions. Our eQTL analysis detected 707 pairs of cis-effect associations (p < 5.64E-06) and 6657 trans-effect associations (p < 3.51E-08), respectively. We also found that top significant cis-eSNPs were enriched around the lncRNA transcription start site regions, and that enrichment patterns of cis-eSNPs differs among different lncRNA sizes (small, medium and large).The constructed SLM interaction networks (1 primary networks and four small separate networks) showed various complex interaction patterns. Especially, the in-depth CIT detected 50 significant lncRNA-mediated SLM trios, and some hotspots (e.g., SNPs: rs926370, rs7716167 and rs16880521; lncRNAs: HIT000061975 and ENST00000579057.1). This study represents the first effort of dissecting the SLM interaction patterns in PBMCs by multi-omics integrative network analysis and causal inference test for clearing the regulation chain. The results provide novel insights into the regulation patterns of lncRNA, and may facilitate investigations of PBMC-related immune physiological process and immunological diseases in the future.
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Department of Statistical, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhu
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Xin-Bo
authors.initials: XB
authors.lastname: Mo
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Guo
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zeng
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Wang
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Qiu
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: He
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Fang-Fei
authors.initials: FF
authors.lastname: Xie
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Bing
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biostatistics and Bioinformatics, Center of Genomics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Neng-Jun
authors.initials: NJ
authors.lastname: Yi
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China. leisf@suda.edu.cn.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China. leisf@suda.edu.cn.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
mesh_terms: D005260:Female; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger