ObjectivesGenome-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.MethodsWe 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.ResultsOur 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.ConclusionsOur results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.

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ABSTRACT. Previous studies have reported associations between the functional FABP2 Ala54Thr (rs1799883) polymorphism and type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome in different populations with conflicting results. We investigated the association between the FABP2 Ala54Thr polymorphism and T2DM (235 cases, 431 controls), obesity (377 cases, 431 controls), and metabolic syndrome (315 cases, 323 controls) by logistic regression analysis in a Chinese study cohort recruited from Yichang, Hubei Province. We then comprehensively reviewed the association of the FABP2 Ala54Thr polymorphism with T2DM, obesity, and metabolic syndrome via meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). The FABP2 Ala54Thr polymorphism was significantly associated with obesity (AT vs AA:Y. Liu et al. 1156©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 1155-1168 (2015) OR = 2.633, 95%CI = 1.065-6.663, P = 0.036; TT vs AA: OR = 4.160, 95%CI = 1.609-10.757, P = 0.003) and metabolic syndrome (TT vs AA: OR = 2.273, 95%CI = 1.242-4.156, P = 0.008) by logistic regression with adjustment for covariates. However, no significant association was found between T2DM and the FABP2 Ala54Thr polymorphism. We identified 24 studies on T2DM (4517 cases, 5224 controls), 9 studies on obesity (949 cases, 2002 controls), and 6 studies on metabolic syndrome (2194 cases, 3282 controls) by literature search. The metaanalyses revealed significant associations for metabolic syndrome (T allele: OR = 1.179, 95%CI = 1.015-1.362, P = 0.031) and T2DM (T allele: OR = 1.160, 95%CI = 1.08-1.24, P < 0.001), but no association for obesity (T allele: OR = 1.069, 95%CI = 0.925-1.235, P = 0.367).