Causal relationship between Alzheimer's disease and unstable angina: a bidirectional Mendelian randomization analysis
Yu-Hang Chen1, Cong-Ying Ren2, Cao Yu3
1Department of Operations Management, Chongqing Mental Health Center, Chongqing, China.
Insights
Alzheimer's disease (AD) significantly increases the risk of unstable angina (UA), according to Mendelian randomization. However, unstable angina does not appear to causally affect Alzheimer's disease risk.
Area of Science:
- Genetics
- Neurology
- Cardiology
Background:
- Observational studies suggest a link between Alzheimer's disease (AD) and cardiovascular disease (CVD).
- The precise genetic underpinnings of AD and coronary heart disease, specifically unstable angina (UA), remain unclear.
- Mendelian randomization (MR) is employed to investigate potential causal genetic relationships.
Purpose of the Study:
- To conduct a bidirectional MR analysis to determine the causal relationship between AD and UA.
- To evaluate the impact of AD on the risk of developing UA.
- To assess if UA genetically influences the risk of AD.
Main Methods:
- Utilized genome-wide association studies (GWAS) from European populations to identify genetic instrumental variables for AD.
- Employed the inverse variance weighted (IVW) approach for primary causal inference.
- Performed sensitivity analyses, including heterogeneity and horizontal pleiotropy assessments, to ensure result validity.
Main Results:
- Genetically predicted AD was associated with an elevated risk of UA (IVW: OR=3.439, P=0.002).
- No significant evidence supported a causal genetic link from UA to AD risk (IVW: OR=0.998, P=0.190).
- Sensitivity analyses confirmed the robustness of findings, showing no significant heterogeneity or horizontal pleiotropy.
Conclusions:
- Alzheimer's disease is identified as a risk factor for unstable angina.
- Further research into the molecular mechanisms connecting AD and UA is warranted.
- Potential for developing personalized treatments based on genetic data is highlighted.
Background:
Research from observational studies has demonstrated a link between Alzheimer's disease (AD) and a higher risk of cardiovascular disease (CVD). Uncertainty surrounds the exact genetic cause of AD and coronary heart disease, particularly unstable angina (UA). Mendelian randomization (MR) analysis was used to examine the causal genetic link between AD and UA to evaluate the impact of AD on UA.
Methods:
The purpose of the bidirectional MR analysis was to investigate the link between exposure and illness causation. Genetic instrumental variables for AD were obtained from European populations using genome-wide association studies (GWAS). The primary causal conclusions were obtained using the inverse variance weighted approach (IVW), and other sensitivity analysis techniques were employed. Sensitivity analyses were carried out to evaluate heterogeneity and horizontal pleiotropy to guarantee accurate MR results.
Results:
An elevated risk of UA was linked to genetically predicted AD (IVW: OR=3.439, 95% CI: 1.565-7.555, P=0.002). A substantial genetic relationship between UA and the risk of AD was not supported by any evidence in the reverse study (IVW: OR=0.998, 95% CI: 0.995-1.001, P=0.190). Various MR techniques produced consistent results. Sensitivity analysis revealed no discernible heterogeneity or horizontal pleiotropy.
Conclusions:
One risk factor for UA that we found in our bidirectional Mendelian randomization trial was AD. This highlights the necessity of researching the underlying molecular mechanisms linked to AD and UA as well as the possibility of creating individualized treatment plans based on genetic data.
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