Objective This study aimed to verify the association between osteoprotegerin gene (OPG) and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based...Objective This study aimed to verify the association between osteoprotegerin gene (OPG) and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis,which integrated all publicly available single-nucleotide polymorphism (SNP)-based P values and obtained an overall P value for the OPG.The significant SNPs were screened for expression quantitative trait loci (eQTLs).Meta-analysis was used to combine the associations between the variants of OPG and bone mineral density (BMD) reported in the literatures.Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of OPG in vitro.Results In the gene-based association analysis,the over all P value of OPG was 6.24×10^-13 for BMD at femoral neck (FN) and 7.37×10^-17 for BMD at lumbar spine (LS),indicating the importance of OPG for OP.The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on OPG at FN and LS.Literature searching found that rs2073617 (known as T950C) was the hot spot SNP.There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed.Significant differences among TT,TC and CC genotypes at FN (P= 0.047) and LS (P= 0.025) were shown by meta-analysis,demonstrating the associations between T950C polymorphism and BMD.Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293T cells (t=-9.47,P<0.01).Conclusion The integrative analysis further confirmed the importance of OPG in OP and the correlation of T950C polymorphism with BMD of OP.The strategy can be used as a reference for functional interpretation of other disease-related genes.展开更多
基金Supported by the National Natural Science Foundation of China(No.31271336)~~
文摘Objective This study aimed to verify the association between osteoprotegerin gene (OPG) and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis,which integrated all publicly available single-nucleotide polymorphism (SNP)-based P values and obtained an overall P value for the OPG.The significant SNPs were screened for expression quantitative trait loci (eQTLs).Meta-analysis was used to combine the associations between the variants of OPG and bone mineral density (BMD) reported in the literatures.Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of OPG in vitro.Results In the gene-based association analysis,the over all P value of OPG was 6.24×10^-13 for BMD at femoral neck (FN) and 7.37×10^-17 for BMD at lumbar spine (LS),indicating the importance of OPG for OP.The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on OPG at FN and LS.Literature searching found that rs2073617 (known as T950C) was the hot spot SNP.There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed.Significant differences among TT,TC and CC genotypes at FN (P= 0.047) and LS (P= 0.025) were shown by meta-analysis,demonstrating the associations between T950C polymorphism and BMD.Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293T cells (t=-9.47,P<0.01).Conclusion The integrative analysis further confirmed the importance of OPG in OP and the correlation of T950C polymorphism with BMD of OP.The strategy can be used as a reference for functional interpretation of other disease-related genes.
