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Exploring the causality of appendectomy and ischaemic heart disease: a Mendelian randomization study and
Shuai Wang1, Tao Zhang1, Yuanlin Sun1
1Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Insights
Appendectomy may increase the risk of ischaemic heart disease (IHD), including acute myocardial infarction (AMI) and angina pectoris (AP). This Mendelian randomization study suggests a potential causal link between appendectomy and these cardiovascular conditions.
Area of Science:
- Cardiovascular Epidemiology
- Genetic Epidemiology
- Surgical Outcomes Research
Background:
- Appendectomy is associated with an increased risk of ischaemic heart disease (IHD), but a causal relationship remains unclear.
- Investigating the causal link between appendectomy and IHD, including acute myocardial infarction (AMI) and angina pectoris (AP), is crucial for understanding cardiovascular disease etiology.
Purpose of the Study:
- To systematically estimate the causal relationship between appendectomy and IHD and its subtypes (AMI, AP) using Mendelian randomization (MR) and meta-analysis.
- To provide robust evidence on whether appendectomy is a risk factor for cardiovascular events.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) design with discovery and replication cohorts.
- Employed genetic variants associated with appendectomy as instrumental variables (IVs) from FinnGen and UK Biobank.
- Performed meta-analyses to combine results and assess the overall causal effect.
Main Results:
- The discovery cohort indicated a significant positive causal relationship between appendectomy and IHD, AMI, and AP.
- The replication cohort confirmed a positive causal relationship between appendectomy and AMI.
- Meta-analysis revealed a significant positive causal relationship between appendectomy and IHD (OR: 1.128), AMI (OR: 1.195), and AP (OR: 1.087).
Conclusions:
- Genetically predicted appendectomy appears to be a risk factor for developing IHD, AMI, and AP.
- These findings highlight the need for continued attention to the potential cardiovascular implications following appendectomy.
Background:
The risk of ischaemic heart disease (IHD) is increased in appendectomy patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between appendectomy and IHD and its subtypes, acute myocardial infarction (AMI) and angina pectoris (AP), using Mendelian randomization (MR) study methods and meta-analysis.
Methods:
As the discovery cohort analysis, we extracted independent genetic variants strongly associated with appendectomy from the FinnGen study (28,601 cases) as instrumental variables (IVs). Genome-wide association study (GWAS) from UK Biobank were selected for outcome data. A first two-sample MR analysis was then conducted. As the replication cohort, IVs associated with appendectomy were extracted in the UK Biobank (50,105 cases). GWAS from the FinnGen study were selected for outcome data. A second MR analysis was then performed. Finally, meta-analyses were applied to assess the combined causal effects of the MR results.
Results:
In the discovery cohort, there was a significant positive causal relationship between appendectomy and IHD and its subtypes AMI and AP. The replication cohort only found a positive causal relationship between appendectomy and AMI. Meta-analysis showed a positive causal relationship between appendectomy and IHD (OR: 1.128, 95% CI: 1.067-1.193, P = 2.459e-05), AMI (OR: 1.195, 95% CI: 1.095-1.305, P = 6.898e-05), and AP (OR: 1.087, 95% CI: 1.016-1.164, P = 1.598e-02).
Conclusions:
This comprehensive MR analysis suggests that genetically predicted appendectomy may be a risk factor for the development of IHD and its subtypes AMI and AP. We need to continue to pay attention to these links.
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