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

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei Ma ◽  
Peilin Li ◽  
Li Liu ◽  
Shiqiang Cheng ◽  
Bolun Cheng ◽  
...  
Keyword(s):  
Femoral Head ◽  
Association Study ◽  
Mrna Expression ◽  
Expression Profiling ◽  
Genome Wide Association Study ◽  
Mrna Level ◽  
Go Analysis ◽  
Genome Wide ◽  
Mrna Expression Profiling ◽  
Go Terms

ObjectiveThis study aims to identify novel candidate genes associated with osteonecrosis of the femoral head (ONFH).MethodsA 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.ResultsTWAS totally identified 564 genes that were with PTWAS value <0.05 for MS and blood, such as CBX1 (PTWAS = 0.0001 for MS), SRPK2 (PTWAS = 0.0002 for blood), and MYO5A (PTWAS = 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 [PTWAS = 0.0270, FC (fold change)mRNA = 7.03], RABEP1 (PTWAS = 0.010, FCmRNA = 2.22), and MORC3 (PTWAS = 0.0053, FCmRNA = 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 (PTWAS = 0.0006, PmRNA = 0.0227), extracellular space (PTWAS = 0.0342, PmRNA = 0.0012), protein binding (PTWAS = 0.0112, PmRNA = 0.0106), and ATP binding (PTWAS = 0.0464, PmRNA = 0.0033).ConclusionSeveral 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.

scholarly journals Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identified Candidate Genes and Pathways Associated With Acute Myocardial Infarction

2021 ◽  
Vol 12 ◽  
Author(s):  
Guanzhong Chen ◽  
Liwei Liu ◽  
Huanqiang Li ◽  
Zhubin Lun ◽  
Ziling Mai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricle ◽  
Association Study ◽  
Mrna Expression ◽  
Expression Profiling ◽  
Enrichment Analysis ◽  
Biological Processes ◽  
Genetic Mechanisms ◽  
Mrna Expression Profiling

BackgroundAcute myocardial infarction (AMI), characterized by an event of myocardial necrosis, is a common cardiac emergency worldwide. However, the genetic mechanisms of AMI remain largely elusive.MethodsA genome-wide association study dataset of AMI was obtained from the CARDIoGRAMplusC4D project. A transcriptome-wide association study (TWAS) was conducted using the FUSION tool with gene expression references of the left ventricle and whole blood. Significant genes detected by TWAS were subjected to Gene Ontology (GO) enrichment analysis. Then the TWAS results of AMI were integrated with mRNA expression profiling to identify common genes and biological processes. Finally, the identified common genes were validated by RT-qPCR analysis.ResultsTWAS identified 1,050 genes for the left ventricle and 1,079 genes for whole blood. Upon comparison with the mRNA expression profile, 4 common genes were detected, including HP (PTWAS = 1.22 × 10–3, PGEO = 4.98 × 10–2); CAMP (PTWAS = 2.48 × 10–2, PGEO = 2.36 × 10–5); TNFAIP6 (PTWAS = 1.90 × 10–2, PGEO = 3.46 × 10–2); and ARG1 (PTWAS = 8.35 × 10–3, PGEO = 4.93 × 10–2). Functional enrichment analysis of the genes identified by TWAS detected multiple AMI-associated biological processes, including autophagy of mitochondrion (GO: 0000422) and mitochondrion disassembly (GO: 0061726).ConclusionThis integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI.

scholarly journals Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse

BMC Genomics ◽  
2007 ◽  
Vol 8 (1) ◽  
pp. 379 ◽  
Author(s):  
Alejandra Rodriguez ◽  
Mika Hilvo ◽  
Leena Kytömäki ◽  
Robert E Fleming ◽  
Robert S Britton ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiling ◽  
Iron Loading ◽  
Genome Wide ◽  
Mrna Expression Profiling

scholarly journals Genome-wide mRNA expression profiling in vastus lateralis of COPD patients with low and normal fat free mass index and healthy controls

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Roberto A Rabinovich ◽  
Ellen Drost ◽  
Jonathan R Manning ◽  
Donald R Dunbar ◽  
MaCarmen Díaz-Ramos ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiling ◽  
Vastus Lateralis ◽  
Fat Free Mass ◽  
Healthy Controls ◽  
Copd Patients ◽  
Genome Wide ◽  
Mrna Expression Profiling

scholarly journals Integrating transcriptome-wide association study and mRNA expression profile identified candidate genes related to hand osteoarthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jiawen Xu ◽  
Yi Zeng ◽  
Haibo Si ◽  
Yuan Liu ◽  
Mingyang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Hand Osteoarthritis ◽  
Mrna Expression Profile ◽  
Knee Oa ◽  
Gene Sets ◽  
Mrna Expression Profiling ◽  
Go Terms

Abstract Background Osteoarthritis (OA) is a common skeletal system disease that has been partially attributed to genetic factors. The hand is frequently affected, which seriously affects the patient’s quality of life. However, the pathogenetic mechanism of hand osteoarthritis (hand OA) is still elusive. Methods A genome-wide association study (GWAS) summary of hand OA was obtained from the UK Biobank dataset, which contains data from a total of 452,264 White British individuals, including 37,782 OA patients. The transcriptome-wide association study (TWAS) of hand OA was performed using FUnctional Summary-based ImputatiON (FUSION) with the skeletal muscle and blood as gene expression references. The significant genes identified by TWAS were further subjected to gene set enrichment analysis (GSEA) with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the genes and gene sets identified by our TWAS with that of a knee OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles in OA. The mRNA expression profiles of 18 normal knee cartilages and 20 OA knee cartilages were acquired from the Gene Expression Omnibus database (accession number: GSE114007). Results TWAS identified 177 genes with P < 0.05 for the skeletal muscle, including ANKRD44 (P = 0.0001), RIC3 (P = 0.0003), and AC005154.6 (P = 0.0004). TWAS identified 423 genes with P < 0.05 for the blood, including CRIM1 (P = 0.0002), ZNF880 (P = 0.0002), and NCKIPSD (P = 0.0003). After comparing the results of the TWAS to those of the mRNA expression profiling of OA, we identified 5 common genes, including DHRS3 (log2fold = − 1.85, P = 3.31 × 10− 9) and SKP2 (log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003) and cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling, including protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS = 0.02, PmRNA = 1.18 × 10− 4), and cytoplasm (PTWAS = 0.0183, PmRNA = 0.0048). Conclusion In this study, we identified 5 candidate genes and 6 GO terms related to hand OA, which may help to uncover the pathogenesis of hand OA. It should be noted that the possible difference in the gene expression profiles between hand OA and knee OA may affect our study results, which should be interpreted with caution.

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