In:
Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-6-7)
Abstract:
This study aims to identify novel candidate genes associated with osteonecrosis of the femoral head (ONFH). Methods A transcriptome-wide association study (TWAS) was performed by integrating the genome-wide association study dataset of osteonecrosis (ON) in the UK Biobank with pre-computed mRNA expression reference weights of muscle skeleton (MS) and blood. The ON-associated genes identified by TWAS were further subjected to gene ontology (GO) analysis by the DAVID tool. Finally, a trans-omics comparative analysis of TWAS and genome-wide mRNA expression profiling was conducted to identify the common genes and the GO terms shared by both DNA-level TWAS and mRNA-level expression profile for ONFH. Results TWAS totally identified 564 genes that were with P TWAS value & lt;0.05 for MS and blood, such as CBX1 ( P TWAS = 0.0001 for MS), SRPK2 ( P TWAS = 0.0002 for blood), and MYO5A ( P TWAS = 0.0005 for blood). After comparing the genes detected by TWAS with the differentially expressed genes identified by mRNA expression profiling, we detected 59 overlapped genes, such as STEAP4 [ P TWAS = 0.0270, FC (fold change) mRNA = 7.03], RABEP1 ( P TWAS = 0.010, FC mRNA = 2.22), and MORC3 ( P TWAS = 0.0053, FC mRNA = 2.92). The GO analysis of TWAS-identified genes discovered 53 GO terms for ON. Further comparing the GO results of TWAS and mRNA expression profiling identified four overlapped GO terms, including cysteine-type endopeptidase activity ( P TWAS = 0.0006, P mRNA = 0.0227), extracellular space ( P TWAS = 0.0342, P mRNA = 0.0012), protein binding ( P TWAS = 0.0112, P mRNA = 0.0106), and ATP binding ( P TWAS = 0.0464, P mRNA = 0.0033). Conclusion Several ONFH-associated genes and GO terms were identified by integrating TWAS and mRNA expression profiling. It provides novel clues to reveal the pathogenesis of ONFH.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2021.663080
DOI:
10.3389/fgene.2021.663080.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606823-0
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