Research method for correlation between cardiovascular disease and vestibular dysfunction

Abstract

The invention discloses a research method for correlation between cardiovascular diseases and vestibular dysfunction, and relates to the technical field of cardiovascular diseases. A new thought is provided for research and treatment of cardiovascular diseases; comprising the following steps: acquiring a GWAS data set of cardiovascular diseases and vestibular dysfunction; sNPs significantly related to cardiovascular diseases are screened as tool variables. According to the method, a double-sample Mendel randomization (MR) technology is adopted, genetic variation is used as a tool variable, and interference of common confounding factors and a reverse causal relationship in traditional observation research is effectively avoided. Strict tool variable screening (such as P value lt; 5 * 10 <-8 >, F statistic is gt; the method can be used for analyzing the causal relationship between the cardiovascular disease and the vestibular dysfunction and various MR analysis methods (such as IVW, MR-Egger, weighted median method and the like), so that the inference accuracy of the causal relationship between the cardiovascular disease and the vestibular dysfunction is remarkably improved.

Description

Technical Field

[0001] The present invention relates to the technical field of cardiovascular diseases, and in particular to a method for studying the correlation between cardiovascular diseases and vestibular dysfunction. Background Art

[0002] As a complex multifactorial disease, the pathogenesis and influencing factors of cardiovascular disease (CVD) have always been a hot topic in medical research. In recent years, with the deepening of genomic research, more and more evidence has shown that genetic factors play an important role in the occurrence and development of cardiovascular disease. As a powerful tool, genome-wide association studies (GWAS) have successfully identified many genetic variants associated with cardiovascular disease, which provide important clues for understanding the biological mechanisms of the disease. On the other hand, vestibular dysfunction, as a common inner ear disease, is mainly manifested by symptoms such as imbalance and vertigo, which seriously affect the quality of life of patients. Although vestibular dysfunction is related to multiple factors such as age, drug use, and inner ear diseases, the role of genetic factors in its onset has gradually attracted attention. Some GWAS studies have found genetic variants associated with vestibular dysfunction, but the potential connection between these variants and cardiovascular disease is still unclear.

[0003] However, direct research on 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. MR analysis is based on the principle of random allocation of genetic variation in the population, which can reduce the impact of confounding factors and thus more accurately assess the causal relationship between exposure factors and outcome variables. In recent years, the emergence of two-sample Mendelian randomization analysis methods has made it possible to use GWAS data from different studies to assess causal relationships.

[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 methods, discuss the potential biological mechanisms and influencing factors between cardiovascular disease and vestibular dysfunction, and provide new ideas for future research and treatment. Summary of the invention

[0005] The purpose of the present invention is to solve the shortcomings of the prior art and to propose a research method for the association between cardiovascular disease and vestibular dysfunction.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for studying the association between cardiovascular disease and vestibular dysfunction, comprising the following steps:

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

[0009] S2: Screening SNPs significantly associated with cardiovascular disease as instrumental variables;

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

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

[0012] S5: The robustness of the results was assessed through sensitivity analysis.

[0013] Preferably, the cardiovascular disease GWAS data include GWAS data of atrial fibrillation, angina pectoris, heart failure, and myocardial infarction. According to the download link or interface provided by the database, the required data set is downloaded, and preliminary data cleaning and sorting are performed.

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

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

[0016] LD pruning was used to exclude highly linked SNPs (r 2 <0.001, kb=10000);

[0017] The F statistic was calculated and SNPs with F>10 were selected as effective instrumental variables.

[0018] Further: The two-sample MR analysis uses five methods, namely, inverse variance weighting (IVW), MR Egger method, weighted median method, simple pattern method and weighted pattern method, to evaluate the causal effect between cardiovascular disease and vestibular dysfunction. Among them, IVW method is the most important analysis method in MR analysis.

[0019] As a preferred solution of the present invention: the reverse MR analysis uses SNPs related to vestibular dysfunction as exposure factors and cardiovascular disease as outcome variables, and is evaluated using IVW, MR-Egger and weighted median methods.

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

[0021] The heterogeneity of the selected SNPs was assessed using the Q test;

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

[0023] As a further embodiment of the present invention: the result interpretation step comprises:

[0024] Determine the causal relationship between cardiovascular disease and vestibular dysfunction;

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

[0026] Potential biological mechanisms and influencing factors are discussed based on the literature.

[0027] Based on the above scheme: the potential biological mechanism includes at least one of inner ear blood circulation obstruction, autonomic nervous dysfunction and inflammatory response.

[0028] The beneficial effects of the present invention are:

[0029] 1. A research method for the association between cardiovascular disease and vestibular dysfunction, using two-sample Mendelian randomization (MR) technology and genetic variation as instrumental variables, effectively avoiding the interference of confounding factors and reverse causality commonly seen in traditional observational studies. Through strict instrumental variable screening (such as P value < 5×10 -8 , F statistic>10) and various MR analysis methods (such as IVW, MR-Egger, weighted median method, etc.) have 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 disease and vestibular dysfunction, which 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 double-sample MR analysis, it revealed a significant genetic causal relationship between angina pectoris, myocardial infarction, coronary atherosclerosis and vestibular dysfunction.

[0031] 3. A research method for the association between cardiovascular disease and vestibular dysfunction not only conducts MR analysis of the effect of cardiovascular disease on vestibular dysfunction, but also explores the effect 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-directional analysis.

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

[0033] 5. A research method for the association between cardiovascular disease and vestibular dysfunction provides an important scientific basis for clinical prevention and treatment by revealing the causal relationship between cardiovascular disease and vestibular dysfunction. The results show that cardiovascular diseases such as angina pectoris, myocardial infarction, and coronary atherosclerosis may cause vestibular dysfunction by affecting the blood circulation in the inner ear. This suggests that clinicians should pay attention to the vestibular function of patients when treating cardiovascular diseases and take corresponding preventive measures. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 It is a flow chart of a research method for the association between cardiovascular disease and vestibular dysfunction proposed by the present invention;

[0035] Figure 2 The present invention proposes a research method for the association between cardiovascular disease and vestibular dysfunction, and provides a summary diagram of MR images obtained according to the IVW method, the MR-Egger method, the simple pattern method, the weighted median method and the weighted pattern method ((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 research method for the association between cardiovascular disease and vestibular dysfunction proposed by the present invention, and a summary diagram of MR images obtained according to the IVW method, MR-Egger method, simple pattern method, weighted median method and weighted pattern method ((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 DESCRIPTION

[0037] The technical solution of this patent is further described in detail below in conjunction with specific implementation methods.

[0038] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0039] Embodiment 1:

[0040] A method for studying the association between cardiovascular disease and vestibular dysfunction, comprising the following steps:

[0041] 1. Data Acquisition

[0042] (1) Cardiovascular disease GWAS data acquisition

[0043] Obtain 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 data set contains sufficient sample size and relevant genetic variation information to meet the needs of subsequent analysis; download the required data set 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) Acquisition of GWAS data on vestibular dysfunction

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

[0047] 2. Instrumental variable screening

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

[0049] PLINK software was used to screen the cardiovascular disease GWAS data and identify SNPs significantly associated with cardiovascular disease (P value < 5 × 10 -8 ); By screening out SNP sites that may be causally related to cardiovascular disease from a large number of genetic variations, they serve as candidate instrumental variables for subsequent analysis;

[0050] (2) Eliminate SNPs in linkage disequilibrium

[0051] Through the LD pruning method, those highly linked SNPs are excluded to reduce redundancy and errors in the analysis; the parameter r is set 2<0.001 and kb = 10000, that is, within a 10 kb range, if the degree of linkage disequilibrium between two SNPs exceeds r 2 =0.001, then one of them is retained as the representative;

[0052] (3) Calculate the F statistic and select effective instrumental variables

[0053] The F statistic of each candidate SNP was calculated to evaluate its validity as an instrumental variable; SNPs with F>10 were selected as effective instrumental variables, which have stronger statistical power and can more accurately reflect the potential causal relationship between cardiovascular disease and vestibular dysfunction;

[0054] 3. MR analysis

[0055] (1) Two-sample MR analysis

[0056] TwoSampleMR R package was used for two-sample Mendelian randomization analysis. The screened effective instrumental variables were used as exposure factors (cardiovascular disease-related SNPs) and vestibular dysfunction was used as the outcome variable for analysis. Inverse variance weighting (IVW), MR-Egger, weighted median method and other methods were used to evaluate the causal relationship between cardiovascular disease and vestibular dysfunction.

[0057] (2) Reverse MR analysis

[0058] In order to explore the effect of vestibular dysfunction on cardiovascular disease, reverse MR analysis was performed; SNPs related to vestibular dysfunction were used as exposure factors and cardiovascular disease was used as outcome variables for analysis; IVW, MR-Egger, weighted median method and other methods were also used for evaluation;

[0059] 4. Sensitivity Analysis

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

[0061] The Q test was used to evaluate the heterogeneity between the selected SNPs; if the Q test result was significant (P value < 0.05), it indicated that there was heterogeneity between the selected SNPs, which may affect the accuracy of MR analysis;

[0062] (2) MR-Egger method to detect horizontal pleiotropy

[0063] The MR-Egger method was used to detect whether the selected SNPs had horizontal pleiotropy; horizontal pleiotropy means that a SNP may affect multiple phenotypes or diseases at the same time, which may lead to bias in MR analysis; if the intercept term of the MR-Egger method was significant (P value < 0.05), it indicated that horizontal pleiotropy may exist;

[0064] 5. 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 disease (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 disease

[0068] Through the results of reverse MR analysis, it is verified whether vestibular dysfunction has an impact on cardiovascular diseases (such as atrial fibrillation, heart failure, etc.); the consistency and robustness of different analysis methods also need to be considered;

[0069] (3) Discussion of potential mechanisms and influencing factors

[0070] Based on the literature and existing studies, the potential biological mechanisms and influencing factors between cardiovascular disease and vestibular dysfunction are discussed; possible mechanisms such as obstructed blood circulation in the inner ear are considered, and the specific effects of different cardiovascular diseases on vestibular function are explored;

[0071] (4) Research limitations and future research directions

[0072] The limitations of this study are discussed, such as sample size, ethnic heterogeneity, age, and gender, and suggestions for future research are proposed, such as conducting larger-scale RCTs to further confirm the causal relationship between cardiovascular disease and vestibular dysfunction, and focusing on vestibular function testing and treatment in people with cardiovascular disease.

[0073] Embodiment 2:

[0074] A research method for the association between cardiovascular diseases and vestibular dysfunction. The results of MR analysis 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 and 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 is a preferred specific implementation manner of the present invention, and the protection scope of the present invention is not limited thereto. Any modification, equivalent substitution and improvement made by any technician familiar with the field within the technical scope disclosed by the present invention in combination with the prior art or public common sense, within the spirit and principle of the present invention, shall be covered by the protection scope of the present invention.

Claims

1. A research method for the association between cardiovascular disease and vestibular dysfunction, characterized in that: The following steps are involved: S1: Access to GWAS datasets for cardiovascular disease and vestibular dysfunction; S2: Screening SNPs significantly associated with cardiovascular disease as instrumental variables; S3: Evaluation of the causal relationship between cardiovascular disease and vestibular dysfunction by two-sample MR analysis; S4: Perform reverse MR analysis to verify the impact of vestibular dysfunction on cardiovascular disease; S5: The robustness of the results was assessed through sensitivity analysis.

2. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 1, characterized in that: The cardiovascular disease GWAS data include GWAS data of atrial fibrillation, angina pectoris, heart failure, and myocardial infarction. According to the download link or interface provided by the database, the required data set is downloaded, and preliminary data cleaning and organization are performed.

3. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 2, characterized in that: The instrumental variable screening step includes: PLINK software was used to screen SNPs significantly associated with cardiovascular disease (P value < 5 × 10 -8 ); LD pruning was used to exclude highly linked SNPs (r 2 <0.001, kb=10000); The F statistic was calculated and SNPs with F>10 were selected as effective instrumental variables.

4. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 3, characterized in that: The two-sample MR analysis uses five methods, namely, inverse variance weighting (IVW), MR Egger method, weighted median method, simple pattern method and weighted pattern method, to evaluate the causal effect between cardiovascular disease and vestibular dysfunction. Among them, IVW method is the most important analysis method in MR analysis.

5. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 4, characterized in that: The reverse MR analysis used vestibular dysfunction-related SNPs as exposure factors and cardiovascular disease as outcome variables, and was evaluated using IVW, MR-Egger, and weighted median methods.

6. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 5, characterized in that: The sensitivity analysis included: The heterogeneity of the selected SNPs was assessed using the Q test; The MR-Egger method was used to detect horizontal pleiotropy. If the intercept term was significant (P value < 0.05), it indicated the existence of horizontal pleiotropy.

7. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 6, characterized in that: The result interpretation step includes: Determine the causal relationship between cardiovascular disease and vestibular dysfunction; Verify the impact of vestibular dysfunction on cardiovascular disease; Potential biological mechanisms and influencing factors are discussed based on the literature.

8. A research method for the association between cardiovascular disease and vestibular dysfunction according to claim 7, characterized in that: The potential biological mechanism includes at least one of inner ear blood circulation obstruction, autonomic nervous system dysfunction and inflammatory response.

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