title: Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction.
abstract: Genome-wide association studies (GWAS) have identified more than sixty single nucleotide polymorphisms (SNPs) associated with increased risk for type 2 diabetes (T2D). However, the identification of causal risk SNPs for T2D pathogenesis was complicated by the factor that each risk SNP is a surrogate for the hundreds of SNPs, most of which reside in non-coding regions. Here we provide a comprehensive annotation of 65 known T2D related SNPs and inspect putative functional SNPs probably causing protein dysfunction, response element disruptions of known transcription factors related to T2D genes and regulatory response element disruption of four histone marks in pancreas and pancreas islet. In new identified risk SNPs, some of them were reported as T2D related SNPs in recent studies. Further, we found that accumulation of modest effects of single sites markedly enhanced the risk prediction based on 1989 T2D samples and 3000 healthy controls. The AROCvalue increased from 0.58 to 0.62 by only using genotype score when putative risk SNPs were added. Besides, the net reclassification improvement is 10.03% on the addition of new risk SNPs. Taken together, functional annotation could provide a list of prioritized potential risk SNPs for the further estimation on the T2D susceptibility of individuals.
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Centre for High Performance Computing, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.
authors.forename: Runyu
authors.initials: R
authors.lastname: Jing
authors.affiliation: College of Life Science, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Qifan
authors.initials: Q
authors.lastname: Kuang
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: College of Computer Science, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gan
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
authors.forename: Menglong
authors.initials: M
authors.lastname: Li
mesh_terms: D019295:Computational Biology / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005091:Exons; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006657:Histones / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D058977:Molecular Sequence Annotation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012045:Regulatory Sequences, Nucleic Acid; D018570:Risk Assessment; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D006657:Histones; D014157:Transcription Factors