Computational analyses of obesity associated loci generated by genome-wide association studies.
Computational analyses of obesity associated loci generated by genome-wide association studies.
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DOI：
10.1371/journal.pone.0199987
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Cheng M;Mei B;Zhou Q;Zhang M;Huang H;Han L;Huang Q
全基因组关联研究（GWAS）发现了许多SNP和基因与肥胖的关联。然而，这些SNP和基因影响肥胖易感性的潜在分子机制仍然没有完全了解。我们的研究目的是通过计算方法全面表征肥胖GWAS SNP和基因。对于肥胖症，分别通过RegulomeDB和3DSNP、miRNASNP和PhosSNP 1.0数据库进行GWAS鉴定的SNP、功能注释、对miRNA结合的影响和对蛋白磷酸化的影响。对于肥胖相关基因，分别用STRING、PANTHER和STRING进行蛋白质相互作用网络构建、基因本体和途径富集分析。在阈值P < 5×10−8时，共有445个SNP与肥胖相关表型显著相关。一些SNPs是肥胖相关基因的eQTLs，一些SNPs位于肥胖相关转录因子的结合位点。确定了可能影响miRNA结合和蛋白质磷酸化的SNP。蛋白质相互作用网络分析确定了高度互连的“枢纽”基因。肥胖相关基因主要参与代谢过程和催化活性，在15条信号通路中显著富集。我们的研究结果为后续的实验测试提供了目标，并进一步阐明了肥胖的病理生理学。
Genome-wide association studies (GWASs) have discovered associations of numerous SNPs and genes with obesity. However, the underlying molecular mechanisms through which these SNPs and genes affect the predisposition to obesity remain not fully understood. Aims of our study are to comprehensively characterize obesity GWAS SNPs and genes through computational approaches. For obesity GWAS identified SNPs, functional annotation, effects on miRNAs binding and impact on protein phosphorylation were performed via RegulomeDB and 3DSNP, miRNASNP, and the PhosSNP 1.0 database, respectively. For obesity associated genes, protein-protein interaction network construction, gene ontology and pathway enrichment analyses were performed by STRING, PANTHER and STRING, respectively. A total of 445 SNPs are significantly associated with obesity related phenotypes at threshold P < 5×10−8. A number of SNPs were eQTLs for obesity associated genes, some SNPs located at binding sites of obesity related transcription factors. SNPs that might affect miRNAs binding and protein phosphorylation were identified. Protein-protein interaction network analysis identified the highly-interconnected “hub” genes. Obesity associated genes mainly involved in metabolic process and catalytic activity, and significantly enriched in 15 signal pathways. Our results provided the targets for follow-up experimental testing and further shed new light on obesity pathophysiology.
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