English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Objective  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 <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.

frontiers in genetics

Integrating Transcriptome-Wide Association Study and mRNA Expression Profiling Identifies Novel Genes Associated With Osteonecrosis of the Femoral Head