Zhu Xiao-Wei, Deng Fei-Yan, Wu Long-Fei, Tang Zai-Xiang, Lei Shu-Feng
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China.
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China.
J Diabetes Complications. 2015 May-Jun;29(4):497-501. doi: 10.1016/j.jdiacomp.2015.02.007. Epub 2015 Feb 20.
Type 2 diabetes (T2D) is a complex endocrine and metabolic disorder, characterized by hyperglycemia due to insulin resistance and relative lack of insulin. Several recent studies have identified a large number of genetic loci associated with T2D without exploring functional mechanisms underlying the associations. This study established integrative analyses to detect the functional mechanisms for T2D-related associations.
Based on the public available datasets and resources, this study performed integrative analyses (gene relationships among implicated loci (GRAIL), expression quantitative trait loci (eQTL) analysis, differential gene expression analysis and functional prediction analysis) to detect the molecular functional mechanisms underlying the associations.
Two single nucleotide polymorphisms (SNPs) (rs7593730, rs2439312) have been found to act as cis-effect regulators of two corresponding eQTL genes (RBMS1, NRG1) among 252 selected (P<E-4) genetic associations that were archived in the public databases. These two non-HLA genes were also differentially expressed in T2D-related cell groups. The two SNPs were predicted as regulatory sites by utilizing online prediction tools.
This study detected potential regulatory mechanisms underlying the associations between T2D and two identified SNPs. Integrative analysis can be used to provide suggestive clues for the molecular functional mechanisms in T2D.
2型糖尿病（T2D）是一种复杂的内分泌和代谢紊乱疾病，其特征是由于胰岛素抵抗和胰岛素相对缺乏导致高血糖。最近的几项研究已经确定了大量与T2D相关的基因位点，但未探索这些关联背后的功能机制。本研究建立了综合分析方法来检测T2D相关关联的功能机制。
基于公开可用的数据集和资源，本研究进行了综合分析（关联位点间基因关系分析（GRAIL）、表达定量性状位点（eQTL）分析、差异基因表达分析和功能预测分析），以检测这些关联背后的分子功能机制。
在公共数据库中存档的252个选定的（P<E-⁴）遗传关联中，发现两个单核苷酸多态性（SNP）（rs7593730、rs2439312）作为两个相应eQTL基因（RBMS1、NRG1）的顺式效应调节因子。这两个非HLA基因在T2D相关细胞组中也存在差异表达。利用在线预测工具将这两个SNP预测为调控位点。
本研究检测到了T2D与两个已鉴定的SNP之间关联背后的潜在调控机制。综合分析可为T2D的分子功能机制提供提示线索。
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