Dataset Information

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children.

ABSTRACT:

Objective

To identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children.

Methods

A tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS was conducted by using FUSION software. Reference panels for muscle skeleton (MS), peripheral blood (NBL) and whole blood (YBL) were used for TWAS analysis. Functional enrichment and protein-protein interaction (PPI) analyses of the genes identified by TWAS were performed by using the online tool Metascape ( http://metascape.org ).

Results

For BMD, we identified 174 genes with P < 0.05, such as IKZF1 (P = 1.46 × 10^-9) and CHKB (P = 8.31 × 10^-7). For LM, we identified 208 genes with P < 0.05, such as COPS5 (P = 3.03 × 10^-12) and MRPS33 (P = 5.45 × 10^-10). Gene ontology (GO) enrichment analysis of the BMD-associated genes revealed 200 GO terms, such as protein catabolic process (Log P = -5.09) and steroid hormone-mediated signaling pathway (Log P = -3.13). GO enrichment analysis of the LM-associated genes detected 287 GO terms, such as the apoptotic signaling pathway (Log P = -8.08) and lipid storage (Log P = -3.55).

Conclusion

This study identified several candidate genes for BMD and LM in children, providing novel clues to the genetic mechanisms underlying the development of childhood BMD and LM.

SUBMITTER: Xu J

PROVIDER: S-EPMC9892108 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children.

Xu Jiawen J Ma Jun J Zeng Yi Y Si Haibo H Wu Yuangang Y Zhang Shaoyun S Shen Bin B

Endocrine 20221227 2

<h4>Objective</h4>To identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children.<h4>Methods</h4>A tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS wa ...[more]

PMID: 36572794

Similar Datasets

Project description:Transcriptome-wide association studies (TWAS) systematically investigate the association of genetically predicted gene expression with disease risk, providing an effective approach to identify novel susceptibility genes. Osteoporosis is the most common metabolic bone disease, associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures, whereas genetic factors explain approximately 70% of the variance in phenotypes associated with bone. BMD is commonly assessed using dual-energy X-ray absorptiometry (DXA) to obtain measurements (g/cm2) of areal BMD. However, quantitative computed tomography (QCT) measured 3D volumetric BMD (vBMD) (g/cm3) has important advantages compared with DXA since it can evaluate cortical and trabecular microstructural features of bone quality, which can be used to directly predict fracture risk. Here, we performed the first TWAS for volumetric BMD (vBMD) by integrating genome-wide association studies (GWAS) data from two independent cohorts, namely the Framingham Heart Study (FHS, n = 3298) and the Osteoporotic Fractures in Men (MrOS, n = 4641), with tissue-specific gene expression data from the Genotype-Tissue Expression (GTEx) project. We first used stratified linkage disequilibrium (LD) score regression approach to identify 12 vBMD-relevant tissues, for which vBMD heritability is enriched in tissue-specific genes of the given tissue. Focusing on these tissues, we subsequently leveraged GTEx expression reference panels to predict tissue-specific gene expression levels based on the genotype data from FHS and MrOS. The associations between predicted gene expression levels and vBMD variation were then tested by MultiXcan, an innovative TWAS method that integrates information available across multiple tissues. We identified 70 significant genes associated with vBMD, including some previously identified osteoporosis-related genes such as LYRM2 and NME8, as well as some novel loci such as DNAAF2 and SPAG16. Our findings provide novel insights into the pathophysiological mechanisms of osteoporosis and highlight several novel vBMD-associated genes that warrant further investigation.

Dataset Information

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children.

Objective

Methods

Results

Conclusion

Publications

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children.

Similar Datasets

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