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Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction
Wu, Yiming1; Jing, Runyu2; Dong, Yongcheng3; Kuang, Qifan1; Li, Yan1; Huang, Ziyan1; Gan, Wei4; Xue, Yue1; Li, Yizhou1; Li, Menglong1
2017-03-06
发表期刊SCIENTIFIC REPORTS
ISSN2045-2322
卷号7页码:11
摘要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 AROC value 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.
DOI10.1038/srep43709
收录类别SCI
语种英语
资助项目National Natural Science Foundation of China[21375095] ; National Natural Science Foundation of China[21305096]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000395545000001
出版者NATURE PUBLISHING GROUP
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://119.78.100.204/handle/2XEOYT63/7513
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Li, Yizhou; Li, Menglong
作者单位1.Sichuan Univ, Coll Chem, Chengdu 610064, Peoples R China
2.Chinese Acad Sci, Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518055, Peoples R China
3.Sichuan Univ, Coll Life Sci, Chengdu 610064, Peoples R China
4.Sichuan Univ, Coll Comp Sci, Chengdu 610064, Peoples R China
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Wu, Yiming,Jing, Runyu,Dong, Yongcheng,et al. Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction[J]. SCIENTIFIC REPORTS,2017,7:11.
APA Wu, Yiming.,Jing, Runyu.,Dong, Yongcheng.,Kuang, Qifan.,Li, Yan.,...&Li, Menglong.(2017).Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction.SCIENTIFIC REPORTS,7,11.
MLA Wu, Yiming,et al."Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction".SCIENTIFIC REPORTS 7(2017):11.
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