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PLoS One ; 11(3): e0150070, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26930606

RESUMO

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.


Assuntos
Predisposição Genética para Doença , MicroRNAs/genética , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos
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