Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HuEx-1_0-st-v2)
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ABSTRACT: Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix 1.0 ST arrays in 73 Caucasian females (age: 47-56) with extremely high (mean ZBMD =1.38, n=42, 16 pre- and 26 postmenopausal subjects) or low hip BMD (mean ZBMD=-1.05, n=31, 15 pre- and 16 postmenopausal subjects). Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects.
Project description:Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects.
Project description:Comparison of circulating monocytes from pre- and postmanopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix HG-133A arrays in 80 Caucasian females, including 40 high (20 pre- and 20 postmanopausal) and 40 low hip BMD (20 pre- and 20 postmanopausal) subjects
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
Project description:Comparison of circulating monocytes from pre- and postmanopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects.
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
Project description:Monocytes were isolated from 30 ml of whole blood from each of 19 women, 10 with high BMD and 9 with low BMD, using monocyte negative isolation kit from Dynal Biotech Inc. Total RNA was extracted from monocytes using Qiagen RNeasy Mini Kit. Targets were produced for each subject using standard Affymetrix procedures from about 4ug of total RNA. Hybridization was made for each subject. Comparison was performed between 10 high BMD and 9 low BMD subjects.
Project description:Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women are more susceptible to experiencing fragility fractures. Our study investigated the associations between circulating proteins with bone mineral density (BMD) in postmenopausal women with or without low BMD (osteoporosis and osteopenia) to explore the pathogenesis of PMOP and discover novel biomarkers for this disease..
Project description:Monocytes were isolated from 30 ml of whole blood from each of 19 women, 10 with high BMD and 9 with low BMD, using monocyte negative isolation kit from Dynal Biotech Inc. Total RNA was extracted from monocytes using Qiagen RNeasy Mini Kit. Targets were produced for each subject using standard Affymetrix procedures from about 4ug of total RNA. Hybridization was made for each subject. Comparison was performed between 10 high BMD and 9 low BMD subjects. Keywords = microarray Keywords = monocyte Keywords = osteoporosis Keywords = HDC Keywords = CCR3 Keywords = GCR Keywords: other