Cargando…

Multi-omics Data Integration for Identifying Osteoporosis Biomarkers and Their Biological Interaction and Causal Mechanisms

Osteoporosis is characterized by low bone mineral density (BMD). The advancement of high-throughput technologies and integrative approaches provided an opportunity for deciphering the mechanisms underlying osteoporosis. Here, we generated genomic, transcriptomic, methylomic, and metabolomic datasets...

Descripción completa

Detalles Bibliográficos
Autores principales: Qiu, Chuan, Yu, Fangtang, Su, Kuanjui, Zhao, Qi, Zhang, Lan, Xu, Chao, Hu, Wenxing, Wang, Zun, Zhao, Lanjuan, Tian, Qing, Wang, Yuping, Deng, Hongwen, Shen, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997862/
https://www.ncbi.nlm.nih.gov/pubmed/32058959
http://dx.doi.org/10.1016/j.isci.2020.100847
Descripción
Sumario:Osteoporosis is characterized by low bone mineral density (BMD). The advancement of high-throughput technologies and integrative approaches provided an opportunity for deciphering the mechanisms underlying osteoporosis. Here, we generated genomic, transcriptomic, methylomic, and metabolomic datasets from 119 subjects with high (n = 61) and low (n = 58) BMDs. By adopting sparse multiple discriminative canonical correlation analysis, we identified an optimal multi-omics biomarker panel with 74 differentially expressed genes (DEGs), 75 differentially methylated CpG sites (DMCs), and 23 differential metabolic products (DMPs). By linking genetic data, we identified 199 targeted BMD-associated expression/methylation/metabolite quantitative trait loci (eQTLs/meQTLs/metaQTLs). The reconstructed networks/pathways showed extensive biomarker interactions, and a substantial proportion of these biomarkers were enriched in RANK/RANKL, MAPK/TGF-β, and WNT/β-catenin pathways and G-protein-coupled receptor, GTP-binding/GTPase, telomere/mitochondrial activities that are essential for bone metabolism. Five biomarkers (FADS2, ADRA2A, FMN1, RABL2A, SPRY1) revealed causal effects on BMD variation. Our study provided an innovative framework and insights into the pathogenesis of osteoporosis.