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Updated: Jan 22, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Discovery of circadian rhythm-related hub genes in acute myocardial infarction: A two-sample Mendelian randomization
Song Peng1,2, Yan Leng3, Man-Hua Chen1,2
1Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Circadian rhythm-related genes impact acute myocardial infarction (AMI) risk. Four risk genes (NR1H3, SREBF1, SIRT1, HIF1A) and one protective gene (NCOA1) were identified, offering new diagnostic and therapeutic insights for AMI.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Chronobiology
Background:
- Circadian rhythms influence physiological processes relevant to cardiovascular disease.
- The specific impact of circadian rhythm-related genes (CRRGs) on acute myocardial infarction (AMI) remains largely unknown.
Purpose of the Study:
- To investigate the association between CRRGs and AMI using genetic data.
- To identify specific CRRGs that act as risk or protective factors for AMI.
Main Methods:
- Utilized two-sample Mendelian randomization (TSMR) analysis on genome-wide association study (GWAS) data for AMI and expression quantitative trait loci (eQTL) data for CRRGs.
- Employed inverse variance weighted (IVW) algorithms to identify hub genes and conducted sensitivity analyses for validation.
- Predicted gene expression in immune cells and tissues using Human Protein Atlas and Genotype-Tissue Expression databases.
Main Results:
- Four CRRGs were identified as risk factors for AMI: NR1H3, SREBF1, SIRT1, and HIF1A.
- One CRRG, NCOA1, was identified as a protective factor for AMI.
- HIF1A, NCOA1, and SREBF1 showed high expression in neutrophils; HIF1A and SREBF1 were also highly expressed in cardiac and arterial tissues.
- NFKB1 was predicted to regulate most identified hub genes, except NCOA1.
Conclusions:
- Identified five key CRRGs (NR1H3, SREBF1, SIRT1, HIF1A, NCOA1) associated with AMI risk and protection.
- These findings provide novel genetic insights into the mechanisms underlying AMI.
- The identified genes and regulatory networks offer potential targets for future diagnostic and therapeutic strategies for AMI.
Abstract:
Circadian rhythms have been reported in a variety of physiological processes that may influence cardiovascular disease, while little is known about the effects of circadian rhythm-related genes (CRRGs) on acute myocardial infarction (AMI). The genome-wide association study (GWAS) data of AMI (ukb-a-533) and expression quantitative trait loci (eQTL) data of CRRGs were downloaded from the integrative epidemiology unit Open GWAS database. The relationship between the CRRGs and AMI was assessed by the two-sample Mendelian randomization (TSMR) analysis. The hub genes that could directly affect AMI were identified based on the inverse variance weighted (IVW) algorithms. Subsequently, the TSMR results were evaluated via sensitivity analyses and MR-Steiger filtering. Then, the expression in immune cells and tissues was predicted from the Human Protein Atlas and Genotype-Tissue Expression databases. Finally, the molecular regulatory networks were generated based on the hub genes. In TSMR results, NR1H3 (IVW: odds ratio (OR) = 1.0009, 95% confidence interval (CI) = 1.0005-1.0013), SREBF1 (IVW: OR = 1.0015, 95% CI = 1.0007-1.0022), SIRT1 (IVW: OR = 1.0007, 95% CI = 1.0001-1.0013), and HIF1A (IVW: OR = 1.0022, 95% CI = 1.0004-1.0039) were risk factors for AMI patients, while NCOA1 (IVW: OR = 0.9984, 95% CI = 0.9969-0.9998) was a protective factor for AMI patients (P < .05). Importantly, the 5 hub genes could affect AMI occurrence in one direction. The expression levels of HIF1A, NCOA1, and SREBF1 were highest in neutrophils than the other immune cells. Also, HIF1A and SREBF1 had higher expression in the heart (left ventricle and atrial appendage) and artery (aorta, tibial, and coronary). Moreover, the transcription factor, NFKB1, might regulate the hub genes except for NCOA1. Generally, 4 risk genes (NR1H3, SREBF1, SIRT1, and HIF1A) and 1 protective gene (NCOA1) associated with circadian rhythm for AMI patients were identified, providing new insights into the diagnosis and treatment of AMI.
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