title: Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses.
abstract: OBJECTIVE
  Type 1 diabetes mellitus (type 1 DM) is an autoimmune disease. Although genome-wide association studies (GWAS) and meta-analyses have successfully identified numerous type 1 DM-associated susceptibility loci, the underlying mechanisms for these susceptibility loci are currently largely unclear.
  
  
  METHODS
  Based on publicly available datasets, we performed integrative analyses (i.e., integrated gene relationships among implicated loci, differential gene expression analysis, functional prediction and functional annotation clustering analysis) and combined with expression quantitative trait loci (eQTL) results to further explore function mechanisms underlying the associations between genetic variants and type 1 DM.
  
  
  RESULTS
  Among a total of 183 type 1 DM-associated SNPs, eQTL analysis showed that 17 SNPs with cis-regulated eQTL effects on 9 genes. All the 9 eQTL genes enrich in immune-related pathways or Gene Ontology (GO) terms. Functional prediction analysis identified 5 SNPs located in transcription factor (TF) binding sites. Of the 9 eQTL genes, 6 (TAP2, HLA-DOB, HLA-DQB1, HLA-DQA1, HLA-DRB5 and CTSH) were differentially expressed in type 1 DM-associated related cells. Especially, rs3825932 in CTSH has integrative functional evidence supporting the association with type 1 DM.
  
  
  CONCLUSIONS
  These findings indicated that integrative analyses can yield important functional information to link genetic variants and type 1 DM.
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, Jiangsu, PR 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, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, Jiangsu, PR 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, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, Jiangsu, PR China.
authors.forename: Zai-Xiang
authors.initials: ZX
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, the Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, Jiangsu, PR China. Electronic address: jiangzh1018@126.com.
authors.forename: Zhen-Huan
authors.initials: ZH
authors.lastname: Jiang
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, Jiangsu, PR China. Electronic address: leisf@suda.edu.cn.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology; D001665:Binding Sites; D056655:Cathepsin H / Q000235:genetics* / Q000276:immunology; D019295:Computational Biology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D063990:Gene Ontology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D040641:Quantitative Trait Loci; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006680:HLA Antigens; D014157:Transcription Factors; C071692:TAP2 protein, human; C534126:CTSH protein, human; D056655:Cathepsin H
keywords: Functional relevance; Immunogenetics; Integrative analyses; Type 1 DM