AUTHOR=Chen Guanzhong , Liu Liwei , Li Huanqiang , Lun Zhubin , Mai Ziling , Lai Wenguang , Chen Enzhao , Zhou Chunyun , Yu Sijia , Yang Junqing , Chen Shiqun , Chen Jiyan , Liu Yong 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.616492

DOI=10.3389/fgene.2021.616492

ISSN=1664-8021

ABSTRACT=Background: Acute 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.
Methods: A 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 qRT-PCR analysis.
Results: TWAS identified 1050 genes for the left ventricle and 1079 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).
Conclusions: This 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.