Dataset Information

Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

ABSTRACT: Osteoporotic fracture (OF) is a serious outcome of osteoporosis. Important risk factors for OF include reduced bone mineral density and unstable bone structure. This genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.Bone mineral density (BMD) and femoral neck cross-sectional geometric parameters (FNCSGPs) are under strong genetic control. DNA copy number variation (CNV) is an important source of genetic diversity for human diseases. This study aims to identify CNVs associated with BMD and FNCSGPs.Genome-wide CNV association analyses were conducted in 1,000 unrelated Caucasian subjects for BMD at the spine, hip, femoral neck, and for three FNCSGPs -cortical thickness (CT), cross-section area (CSA), and buckling ratio (BR). BMD was measured by dual energy X-ray absorptiometry (DEXA). CT, CSA, and BR were estimated using DEXA measurements. Affymetrix 500K arrays and copy number analysis tool was used to identify CNVs.A CNV in VPS13B gene was significantly associated with spine, hip and FN BMDs, and CT, CSA, and BR (p < 0.05). Compared to subjects with two copies of the CNV, carriers of one copy had an average of 14.6%, 12.4%, and 13.6% higher spine, hip, and FN BMD, 20.0% thicker CT, 10.6% larger CSA, and 12.4% lower BR. Thus, a decrease of the CNV consistently produced stronger bone, thereby reducing osteoporotic fracture risk.VPS13B gene, via affecting BMD and FNCSGPs, is a novel osteoporosis risk gene.

SUBMITTER: Deng FY

PROVIDER: S-EPMC2924432 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

Deng F-Y FY Zhao L-J LJ Pei Y-F YF Sha B-Y BY Liu X-G XG Yan H H Wang L L Yang T-L TL Recker R R RR Papasian C J CJ Deng H-W HW

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20090813 4

<h4>Unlabelled</h4>Osteoporotic fracture (OF) is a serious outcome of osteoporosis. Important risk factors for OF include reduced bone mineral density and unstable bone structure. This genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.<h4>Introduction</h4>Bone mineral density (BMD) and femoral neck cross-sectional geometric parameters (FNCSGPs) are under strong genetic control. DNA copy number variation (CNV) is an important source of geneti ...[more]

PMID: 19680589

Similar Datasets

Project description:The human genome displays extensive copy-number variation (CNV). Recent discoveries have shown that large segments of DNA, ranging in size from hundreds to thousands of nucleotides, are either deleted or duplicated. This CNV may encompass genes, leading to a change in phenotype, including drug response phenotypes. Gemcitabine and 1-beta-D-arabinofuranosylcytosine (AraC) are cytidine analogues used to treat a variety of cancers. Previous studies have shown that genetic variation may influence response to these drugs. In the present study, we set out to test the hypothesis that variation in copy number might contribute to variation in cytidine analogue response phenotypes.We used a cell-based model system consisting of 197 ethnically-defined lymphoblastoid cell lines for which genome-wide SNP data were obtained using Illumina 550 and 650 K SNP arrays to study cytidine analogue cytotoxicity. 775 CNVs with allele frequencies > 1% were identified in 102 regions across the genome. 87/102 of these loci overlapped with previously identified regions of CNV. Association of CNVs with gemcitabine and AraC IC50 values identified 11 regions with permutation p-values < 0.05. Multiplex ligation-dependent probe amplification assays were performed to verify the 11 CNV regions that were associated with this phenotype; with false positive and false negative rates for the in-silico findings of 1.3% and 0.04%, respectively. We also had basal mRNA expression array data for these same 197 cell lines, which allowed us to quantify mRNA expression for 41 probesets in or near the CNV regions identified. We found that 7 of those 41 genes were highly expressed in our lymphoblastoid cell lines, and one of the seven genes (SMYD3) that was significant in the CNV association study was selected for further functional experiments. Those studies showed that knockdown of SMYD3, in pancreatic cancer cell lines increased gemcitabine and AraC resistance during cytotoxicity assay, consistent with the results of the association analysis.These results suggest that CNVs may play a role in variation in cytidine analogue effect. Therefore, association studies of CNVs with drug response phenotypes in cell-based model systems, when paired with functional characterization, might help to identify CNV that contributes to variation in drug response.

Dataset Information

Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

Publications

Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets