Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.
Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.
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全基因组关联研究鉴定的骨质疏松症相关 SNP 和基因的计算特征
DOI：
10.1371/journal.pone.0150070
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发表时间：
2016
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：
Qin L;Liu Y;Wang Y;Wu G;Chen J;Ye W;Yang J;Huang Q
全基因组关联研究（GWASs）揭示了许多与骨质疏松症相关的SNP和基因。然而，这些SNP和基因对骨质疏松症易感性的影响尚未完全了解。本研究的目的是鉴定可能影响转录因子和miRNA结合亲和力的骨质疏松症GWAS相关SNPs，揭示骨质疏松症GWAS相关基因的富集信号通路和“中枢”基因。我们进行了多项计算分析，以探索骨质疏松症GWAS相关SNP和基因的功能和机制，包括SNP保守性分析和功能注释（SNP对转录因子和miRNA结合的影响），基因本体分析，通路分析和蛋白质-蛋白质相互作用分析。我们的研究结果表明，一些SNPs可能影响转录因子（NFATC 2，MEF 2C，SOX 9，RUNX 2，ESR 2，FOXA 1和STAT 3）和miRNA的结合亲和力。骨质疏松症GWASs相关基因中，Wnt信号通路、基底细胞癌和Hedgehog信号通路的表达明显增加。通过相互作用网络分析揭示了高度互连的“枢纽”基因是RUNX 2、SP 7、TNFRSF 11B、LRP 5、DKK 1、ESR 1和SOST。我们的研究结果为进一步的实验评估和进一步了解骨质疏松症的病理生理提供了目标。
Genome-wide association studies (GWASs) have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and “hub” genes of osteoporosis GWAS-associated genes. We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding), gene ontology analysis, pathway analysis and protein-protein interaction analysis. Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3) and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected “hub” genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST. Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.