Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies

PLoS One. 2016 Mar 1;11(3):e0150070. doi: 10.1371/journal.pone.0150070. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • MicroRNAs / genetics*
  • Osteoporosis / genetics*
  • Polymorphism, Single Nucleotide*
  • Transcription Factors / genetics*

Substances

  • MicroRNAs
  • Transcription Factors

Grants and funding

This work was supported by National Natural Science Foundation of China (Nos. 31371275 and 30971635) and self-determined research funds of CCNU from the colleges’ basic research and operation of MOE (No. CCNU14Z01003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.