A method for studying the association of cardiovascular disease with vestibular dysfunction

Abstract

The application discloses a research method for cardiovascular diseases and vestibular dysfunction, and relates to the technical field of cardiovascular diseases; in order to provide a new idea for the research and treatment of cardiovascular diseases; comprising the following steps: obtaining GWAS data sets of cardiovascular diseases and vestibular dysfunction; screening SNPs significantly related to cardiovascular diseases as instrumental variables. The application adopts Mendelian randomization (MR) technology of double samples, uses genetic variation as an instrumental variable, effectively avoids the interference of common confounding factors and reverse causal relationship in traditional observational research. Through strict instrumental variable screening (such as P value < 5x10 ‑8 , F-statistic > 10) and various MR analysis methods (such as IVW, MR-Egger, weighted median method, etc.), the accuracy of the causal relationship between cardiovascular diseases and vestibular dysfunction is significantly improved.

Description

Technical Field

[0001] This invention relates to the field of cardiovascular disease technology, and in particular to a research method for the association between cardiovascular disease and vestibular dysfunction. Background Technology

[0002] Cardiovascular disease (CVD), as a complex multifactorial disease, has always been a hot topic in medical research regarding its pathogenesis and influencing factors. In recent years, with the deepening of genomics research, increasing evidence suggests that genetic factors play an important role in the occurrence and development of CVD. Genome-wide association studies (GWAS), as a powerful tool, have successfully identified numerous genetic variants associated with CVD, providing important clues for understanding the biological mechanisms of the disease. On the other hand, vestibular dysfunction, a common inner ear disease, mainly manifests as balance disorders, dizziness, and other symptoms, seriously affecting patients' quality of life. Although vestibular dysfunction is related to various factors such as age, medication use, and inner ear diseases, the role of genetic factors in its pathogenesis is gradually attracting attention. Some GWAS studies have identified genetic variants associated with vestibular dysfunction, but the potential link between these variants and CVD remains unclear.

[0003] However, directly studying the causal relationship between cardiovascular disease and vestibular dysfunction faces many challenges. On the one hand, these two diseases involve complex physiological and pathological processes, and their interaction mechanisms are difficult to observe directly. On the other hand, traditional observational research methods are easily affected by confounding factors, making it difficult to accurately assess causal relationships. Mendelian randomization (MR) analysis, as a statistical method that uses genetic variation as an instrumental variable to assess causal relationships, provides a new approach to solving this problem. Based on the principle of random allocation of genetic variation in the population, MR analysis can reduce the influence of confounding factors, thereby more accurately assessing the causal relationship between exposure factors and outcome variables. In recent years, the emergence of two-sample Mendelian randomization analysis has made it possible to assess causal relationships using GWAS data from different studies.

[0004] Therefore, this study aims to explore the potential causal relationship between cardiovascular disease and vestibular dysfunction using GWAS data and two-sample Mendelian randomization analysis, and to discuss the potential biological mechanisms and influencing factors between cardiovascular disease and vestibular dysfunction, so as to provide new ideas for future research and treatment. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing a research method for the association between cardiovascular diseases and vestibular dysfunction.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A research method for identifying the association between cardiovascular disease and vestibular dysfunction includes the following steps:

[0008] S1: Obtain GWAS datasets for cardiovascular disease and vestibular dysfunction;

[0009] S2: Screen SNPs that are significantly associated with cardiovascular disease as instrumental variables;

[0010] S3: Assess the causal relationship between cardiovascular disease and vestibular dysfunction using two-sample MR analysis;

[0011] S4: Perform reverse MR analysis to verify the impact of vestibular dysfunction on cardiovascular disease;

[0012] S5: Assess the robustness of the results through sensitivity analysis.

[0013] Preferably, the cardiovascular disease GWAS data includes GWAS data for atrial fibrillation, angina pectoris, heart failure, and myocardial infarction. The required dataset is downloaded according to the download link or interface provided by the database, and preliminary data cleaning and organization are performed.

[0014] Furthermore: the instrumental variable screening step includes:

[0015] PLINK software was used to screen for SNPs significantly associated with cardiovascular disease (P < 5 × 10⁻⁶). -8 );

[0016] Highly linked SNPs were excluded by chain unbalanced pruning (LD pruning). 2 <0.001, kb=10000);

[0017] Calculate the F-statistic and select SNPs with F>10 as effective instrumental variables.

[0018] Furthermore, the two-sample MR analysis employed five methods to assess the causal effect between cardiovascular disease and vestibular dysfunction: inverse variance weighted (IVW), MR Egger method, weighted median method, simple pattern method, and weighted pattern method. Among these, the IVW method is the most important analytical method in the MR analysis.

[0019] As a preferred embodiment of the present invention, the reverse MR analysis uses vestibular dysfunction-related SNPs as exposure factors and cardiovascular disease as an outcome variable, and employs methods such as IVW, MR-Egger, and weighted median method for evaluation.

[0020] As a further aspect of the present invention: the sensitivity analysis includes:

[0021] The Q test was used to assess the heterogeneity of the selected SNPs;

[0022] The MR-Egger method was used to detect level pleiotropy. If the intercept term was significant (P value < 0.05), it indicated the presence of level pleiotropy.

[0023] As a further aspect of the present invention: the result interpretation step includes:

[0024] To establish a causal relationship between cardiovascular disease and vestibular dysfunction;

[0025] To verify the impact of vestibular dysfunction on cardiovascular disease;

[0026] The potential biological mechanisms and influencing factors are discussed in conjunction with the literature.

[0027] Based on the aforementioned scheme: the potential biological mechanisms include at least one of inner ear blood circulation obstruction, autonomic nervous system dysfunction, and inflammatory response.

[0028] The beneficial effects of this invention are as follows:

[0029] 1. A research method for the association between cardiovascular disease and vestibular dysfunction, employing two-sample Mendelian randomization (MR) technology and utilizing genetic variation as an instrumental variable, effectively avoids the interference of confounding factors and reverse causality commonly found in traditional observational studies. This is achieved through rigorous instrumental variable screening (e.g., p-value < 5 × 10⁻⁶). -8 The use of F-statistics > 10 and various MR analysis methods (such as IVW, MR-Egger, weighted median method, etc.) significantly improved the accuracy of inferring the causal relationship between cardiovascular disease and vestibular dysfunction.

[0030] 2. A research method for the association between cardiovascular diseases and vestibular dysfunction systematically explored the causal relationship between various cardiovascular diseases (such as atrial fibrillation, angina pectoris, heart failure, myocardial infarction, hypertension, and coronary atherosclerosis) and vestibular dysfunction. Through two-sample MR analysis, a significant genetic causal relationship between angina pectoris, myocardial infarction, coronary atherosclerosis, and vestibular dysfunction was revealed.

[0031] 3. A research method for the association between cardiovascular disease and vestibular dysfunction not only conducted MR analysis on the effect of cardiovascular disease on vestibular dysfunction, but also explored the impact of vestibular dysfunction on cardiovascular disease through reverse MR analysis, further enhancing the reliability of causal inference and avoiding the bias that may be caused by single-direction analysis.

[0032] 4. A research method for the association between cardiovascular disease and vestibular dysfunction, based on publicly available GWAS databases (such as IEU Open GWAS and FinnGen), avoids the high cost and time-consuming problems of sample collection in traditional studies. Through the analysis of large-scale data and rigorous statistical methods, it achieves an efficient and low-cost research design.

[0033] 5. A research method for the association between cardiovascular diseases and vestibular dysfunction. By revealing the causal relationship between cardiovascular diseases and vestibular dysfunction, this study provides important scientific evidence for clinical prevention and treatment. The results show that cardiovascular diseases such as angina pectoris, myocardial infarction, and coronary atherosclerosis may lead to vestibular dysfunction by affecting blood circulation in the inner ear. This suggests that clinicians should pay attention to patients' vestibular function when treating cardiovascular diseases and take corresponding preventive measures. Attached Figure Description

[0034] Figure 1 This is a flowchart illustrating a research method for the association between cardiovascular disease and vestibular dysfunction proposed in this invention.

[0035] Figure 2 This is a summary of MR images obtained using the IVW method, MR-Egger method, simple pattern method, weighted median method, and weighted pattern method, based on a research method for the association between cardiovascular diseases and vestibular dysfunction proposed in this invention. (A) MR analysis results of atrial fibrillation and vestibular dysfunction. (B) MR analysis results of heart failure and vestibular dysfunction. (C) MR analysis results of angina pectoris and vestibular dysfunction. (D) MR analysis results of myocardial infarction and vestibular dysfunction. (E) MR analysis results of hypertension and vestibular dysfunction. (F) MR analysis results of coronary atherosclerosis and vestibular dysfunction.

[0036] Figure 3 This is a summary of MR images obtained using the IVW method, MR-Egger method, simple mode method, weighted median method, and weighted mode method, based on a research method for the association between cardiovascular diseases and vestibular dysfunction proposed in this invention. (A) MR analysis results of vestibular dysfunction and atrial fibrillation. (B) MR analysis results of vestibular dysfunction and heart failure. (C) MR analysis results of vestibular dysfunction and angina pectoris. (D) MR analysis results of vestibular dysfunction and myocardial infarction. (E) MR analysis results of vestibular dysfunction and hypertension. (F) MR analysis results of vestibular dysfunction and coronary atherosclerosis. Detailed Implementation

[0037] The technical solution of this patent will be further described in detail below with reference to specific embodiments.

[0038] The embodiments of this patent are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this patent, and should not be construed as limiting this patent.

[0039] Example 1:

[0040] A research method for identifying the association between cardiovascular disease and vestibular dysfunction includes the following steps:

[0041] Part 1: Data Acquisition

[0042] (1) Acquisition of GWAS data for cardiovascular diseases

[0043] Retrieve relevant data from the IEU Open GWAS database;

[0044] Select GWAS data for atrial fibrillation, angina pectoris, heart failure, and myocardial infarction; ensure that the dataset contains a sufficient sample size and relevant genetic variation information to meet the needs of subsequent analysis; download the required dataset according to the download link or interface provided by the database, and perform preliminary data cleaning and organization to ensure the accuracy and completeness of the data;

[0045] (2) GWAS data acquisition for vestibular dysfunction

[0046] Obtain GWAS data on vestibular dysfunction from the FinnGen database (R10 version); ensure that the dataset contains a sufficient number of samples and relevant genetic variation information, especially SNPs (single nucleotide polymorphisms) sites associated with vestibular dysfunction; download the required dataset and perform data cleaning and organization.

[0047] II. Instrumental Variable Selection

[0048] (1) Screening for SNPs significantly associated with cardiovascular disease

[0049] The PLINK software was used to screen cardiovascular disease GWAS data to identify SNPs (P-value < 5 × 10⁻⁶) that were significantly associated with cardiovascular disease. -8 ); By screening a large number of genetic variations, SNP sites that may have a causal relationship with cardiovascular disease are selected as candidate instrumental variables for subsequent analysis;

[0050] (2) Exclude SNPs with linkage disequilibrium

[0051] The LD pruning (linkage imbalance pruning) method is used to exclude highly linked SNPs, thereby reducing redundancy and errors in the analysis; the parameter r is set... 2<0.001 and kb=10000, that is, within the range of 10kb, if the degree of linkage disequilibrium between two SNPs exceeds r 2 If the value is 0.001, then one of them is retained as a representative.

[0052] (3) Calculate the F-statistic and screen for effective instrumental variables.

[0053] Calculate the F-statistic for each candidate SNP to assess its effectiveness as an instrumental variable; select SNPs with F>10 as effective instrumental variables, as these variables have stronger statistical power and can more accurately reflect the potential causal relationship between cardiovascular disease and vestibular dysfunction.

[0054] III. MR Analysis

[0055] (1) Two-sample MR analysis

[0056] Two-sample Mendelian randomization analysis was performed using the TwoSampleMR R package; the selected effective instrumental variables were used as exposure factors (cardiovascular disease-related SNPs), and vestibular dysfunction was used as the outcome variable for analysis; the causal relationship between cardiovascular disease and vestibular dysfunction was assessed using various methods such as inverse variance weighting (IVW), MR-Egger, and weighted median method.

[0057] (2) Reverse MR analysis

[0058] To investigate the impact of vestibular dysfunction on cardiovascular disease, a reverse MR analysis was performed. Vestibular dysfunction-related SNPs were used as exposure factors, and cardiovascular disease was used as an outcome variable. The analysis was conducted using methods such as IVW, MR-Egger, and weighted median.

[0059] IV. Sensitivity Analysis

[0060] (1) Q test to assess the heterogeneity of SNPs

[0061] The Q test is used to assess the heterogeneity among the selected SNPs; if the Q test result is significant (P value < 0.05), it indicates that there is heterogeneity among the selected SNPs, which may affect the accuracy of MR analysis.

[0062] (2) MR-Egger method for detecting level pleiotropy

[0063] The MR-Egger method was used to detect whether the selected SNPs exhibited level pleiotropy. Level pleiotropy refers to the fact that a single SNP may simultaneously affect multiple phenotypes or diseases, which may lead to bias in MR analysis. If the intercept term of the MR-Egger method is significant (P value < 0.05), it indicates that level pleiotropy may exist.

[0064] V. Interpretation of Results

[0065] (1) Determine the causal relationship between cardiovascular disease and vestibular dysfunction.

[0066] Based on the results of MR analysis, determine whether there is a significant causal relationship between cardiovascular diseases (such as angina pectoris, myocardial infarction, etc.) and vestibular dysfunction; consider the consistency and robustness of different analysis methods (such as IVW, MR-Egger, weighted median method);

[0067] (2) Verify the impact of vestibular dysfunction on cardiovascular diseases

[0068] The results of reverse MR analysis were used to verify whether vestibular dysfunction affects cardiovascular diseases (such as atrial fibrillation, heart failure, etc.); the consistency and robustness of different analytical methods also need to be considered.

[0069] (3) Discuss potential mechanisms and influencing factors

[0070] Based on literature and existing research, this study discusses the potential biological mechanisms and influencing factors between cardiovascular diseases and vestibular dysfunction; it considers possible mechanisms such as obstruction of blood circulation in the inner ear and explores the specific effects of different cardiovascular diseases on vestibular function.

[0071] (4) Limitations of the research and future research directions

[0072] This paper discusses the limitations of this study, such as sample size, racial heterogeneity, age, and gender. It also proposes directions and suggestions for future research, such as conducting larger-scale RCT experiments to further confirm the causal relationship between cardiovascular disease and vestibular dysfunction, and focusing on vestibular function testing and treatment in cardiovascular disease populations.

[0073] Example 2:

[0074] A research method for the association between cardiovascular diseases and vestibular dysfunction. The MR analysis results of atrial fibrillation, heart failure, angina pectoris, myocardial infarction, hypertension and coronary atherosclerosis with vestibular dysfunction are shown in Table 1.

[0075]

[0076]

[0077]

[0078]

[0079] Table 1

[0080] The MR analysis results of vestibular dysfunction in relation to atrial fibrillation, heart failure, angina pectoris, myocardial infarction, hypertension, and coronary atherosclerosis are shown in Table 2:

[0081]

[0082]

[0083]

[0084]

[0085] Table 2

[0086] The above description represents a preferred embodiment of the present invention. The scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, and improvements made by those skilled in the art within the scope of the technology disclosed in the present invention, combined with existing technology or common knowledge, and within the spirit and principles of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A research method for the association between cardiovascular disease and vestibular dysfunction, characterized in that, Includes the following steps: S1: Obtain GWAS datasets for cardiovascular disease and vestibular dysfunction; S2: Screen SNPs that are significantly associated with cardiovascular disease as instrumental variables; S3: Assess the causal relationship between cardiovascular disease and vestibular dysfunction using two-sample MR analysis; S4: Perform reverse MR analysis to verify the impact of vestibular dysfunction on cardiovascular disease; S5: Assess the robustness of the results through sensitivity analysis; The instrumental variable selection step includes: Use PLINK software to screen for SNPs that are significantly associated with cardiovascular disease; Highly linked SNPs were eliminated by chain unbalanced pruning (LD pruning); Calculate the F-statistic and screen SNPs with F>10 as effective instrumental variables; The two-sample MR analysis used five methods to assess the causal effect between cardiovascular disease and vestibular dysfunction: inverse variance weighted method (IVW), MR Egger method, weighted median method, simple pattern method, and weighted pattern method. Among them, the IVW method is the most important analytical method in the MR analysis. The reverse MR analysis used vestibular dysfunction-related SNPs as exposure factors and cardiovascular disease as an outcome variable, and employed IVW, MR-Egger and weighted median methods for assessment. The sensitivity analysis includes: The Q test was used to assess the heterogeneity of the selected SNPs; The MR-Egger method was used to detect level pleiotropy. If the intercept term was significant, it indicated the presence of level pleiotropy.

2. The research method for the association between cardiovascular disease and vestibular dysfunction according to claim 1, characterized in that, The cardiovascular disease GWAS data includes GWAS data for atrial fibrillation, angina pectoris, heart failure, and myocardial infarction. Download the required dataset according to the download link or interface provided by the database, and perform preliminary data cleaning and organization.

3. The research method for the association between cardiovascular disease and vestibular dysfunction according to claim 2, characterized in that, The result interpretation steps include: To establish a causal relationship between cardiovascular disease and vestibular dysfunction; To verify the impact of vestibular dysfunction on cardiovascular disease; The potential biological mechanisms and influencing factors are discussed in conjunction with the literature.

4. The research method for the association between cardiovascular disease and vestibular dysfunction according to claim 3, characterized in that, The potential biological mechanisms include at least one of inner ear blood circulation obstruction, autonomic nervous system dysfunction, and inflammatory response.

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