(MR-Egger regression)
No statistical relationship was found between SM and the risk of VVs. The MR results for the 11 types of SM with VVs are shown in Table Table5 5 .
Associations between the genetically predicted plasma levels of SM and the risk of VVs.
Risk factors | -value (IVW) |
---|---|
SM (d32:1) | .555892570424861 |
SM (d34:0) | .607688319668095 |
SM (d34:1) | .644496431471553 |
SM (d34:2) | .767938398521698 |
SM (d36:1) | .608328749809907 |
SM (d36:2) | .0568243756446325 |
SM (d38:1) | .961835090085724 |
SM (d38:2) | .944556249031821 |
SM (d40:1) | .227288510703765 |
SM (d40:2) | .879874536677981 |
SM (d42:2) | .956958845599248 |
IVW = inverse-variance weighted, SM = sphingomyelin.
Overall, these results support a potential causal relationship between specific types of lipid levels and the risk of VVs.
This study’s findings reveal potential aspects of the pathogenesis of VVs, emphasizing the role of specific lipid molecules. The results suggest a potential causal relationship between certain types of lipid levels and the risk of VVs. Some lipids, such as PC (15:0_18:1) and PE (O-16:1_20:4), showed significant positive or negative correlations with the risk of VVs. However, for other lipids, this association might be weaker or not significant. These findings provide important clues for future studies on biological mechanisms and potential preventive or therapeutic strategies.
The current understanding of the relationship between plasma lipids and the risk of VVs requires further research. Our study extends existing knowledge about VVs, highlighting the potential causal relationship between specific plasma lipid components and the development of VVs. Previous research by H. Tanaka et al using imaging mass spectrometry revealed a unique lipid distribution in primary varicose veins. They found increased concentrations of PC, Lyso-phosphatidylcholine (LPC), and SM around the veins in patients with VVs[. [ 16 ] LPC is associated with inflammation, being a chemotactic factor for macrophages and lymphocytes, known to induce the expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) in endothelial cells. Due to its detergent-like properties, high concentrations of LPC can lyse cells. The specific localization of LPC on the valves of VV tissues suggests that the valves could be damaged due to LPC-induced inflammation or its detergent-like properties. [ 22 ] SM is a precursor of sphingolipid mediators. Over 36 studies have shown that sphingolipid mediators, including ceramides and ceramide 1-phosphate, play an indispensable role in the inflammatory process. The accumulation of PC (1-acyl 36:4) and SM (d18:1/16:0) around the valvular areas may severely exacerbate tissue inflammation around varicose vein valves. Valve dysfunction leads to venous reflux, thereby leading to the development of varicose veins. These lipids are related to inflammation and cellular pathways. The aggregation of PC can lead to the aggregation of phospholipase and its decomposition into LPC and free fatty acids. Furthermore, a study by Anwar et al using analytical techniques provided a comprehensive metabolic profile of the disease. In their study, compared with the non-varicose vein group, the lipid extracts from varicose vein group had higher concentrations of PC, PE, and SM. Pathway analysis indicates that PC and SM are associated with inflammation, while inositol is related to cell proliferation. [ 6 ] SM, PC, phosphocholine, ceramide, and diacylglycerol influence cell survival, with the first 3 promoting growth and survival, and the latter 2 inducing cell death and quiescence. [ 23 , 24 ] This suggests that the local chemical environment and physical stress cells experience following chronic blood stasis could trigger changes in metabolic balance and disrupt lipid homeostasis, leading to the production of certain pro-survival molecules and their downstream effects.
Despite the advantages of well-designed, large-scale prospective studies, they are still susceptible to the effects of residual confounding and reverse causation. Therefore, our study employed MR analysis to explore the relationship between plasma lipid levels and the risk of VVs. In MR analysis, plasma lipid levels are determined genetically; thus, they are not influenced by confounding factors. Utilizing large-scale GWAS data for a two-sample MR analysis provides a more robust method of establishing causality compared to traditional observational studies. The association between 12 types of lipids and the risk of VVs reached statistical significance across various MR analysis methods, enhancing the robustness of these findings. Particularly, when both the IVW and the weighted median methods showed similar significant results, it provided reliable evidence to support the study. For some lipid types, a higher P -value in MR-Egger might indicate potential pleiotropy bias. Careful consideration should be given to potential biases and other confounding factors when interpreting these relationships. Overall, these results support a potential causal relationship between specific types of lipid levels and the risk of VVs. Moreover, the introduction of BWMR addressed potential biases more effectively than traditional MR methods, enhancing the reliability of our findings. The detection of pleiotropy and heterogeneity also supports the robustness and reliability of our results.
Previous research has highlighted the potential role of lipid molecules in the development of VVs, particularly in relation to inflammation and cellular pathways. We have further expanded the research in this area, proposing not only the potential causal relationship between PC and PE types of lipids and VVs but also identifying an association with specific types of PI. Our study provides causal evidence for the role of these lipids in the development of VVs through genetic methods. Although our research did not find a potential causal relationship between SM and VVs, this does not negate the role of SM in the inflammatory process, as was also shown in the studies by Tanaka et al. The differences may stem from the design and analytical methods of our study, highlighting the need for further research to fully understand the complex roles of different lipid molecules in the development of VVs.
This study has some limitations. First, the accuracy of MR analysis highly depends on the validity of the chosen instrumental variables (SNPs). These SNPs must be strongly associated with the exposure and affect the outcome variable only through the exposure. If there are other pathways affecting the outcome, such as horizontal pleiotropy, it might lead to bias. Second, genetic heterogeneity between populations could affect the generalizability of the relationship between SNPs and the exposure, and the GWAS data used in this study primarily come from a specific population (European descent), so the results may not be directly generalizable to people of other backgrounds. Third, MR analysis often assumes a linear relationship between exposure and outcome. If the actual relationship is nonlinear, this simplification could lead to incorrect conclusions. Finally, the quality and accuracy of MR analysis also depend on the quality and availability of the underlying GWAS studies. Any errors or deficiencies in the data could affect the outcomes of the MR analysis. Even if MR analysis indicates a causal relationship, identifying the specific biological mechanisms remains a challenge. Additionally, MR analysis cannot provide information on the size of intervention effects. [ 17 ] Overall, while this study provides valuable insights, these limitations should be considered when interpreting the results and generalizing the findings. Future research may need to be conducted across multiple populations and combined with experimental studies to further validate causal relationships and clarify biological mechanisms.
In conclusion, this study not only advances our understanding of the pathophysiology of VVs but also highlights the potential of lipid molecules as biomarkers and therapeutic targets in vascular diseases. The potential causal links pave the way for further investigation into lipid metabolism’s role in VVs, offering insights for more effective management of this condition.
Conceptualization: Haibin Yu.
Data curation: Kailin Shen, Haibin Yu.
Methodology: Kailin Shen, Haibin Yu.
Resources: Kailin Shen.
Software: Kailin Shen.
Supervision: Fangtao Zhu, Cunwei Cheng, Haibin Yu.
Validation: Kailin Shen.
Visualization: Kailin Shen.
Writing – original draft: Kailin Shen, Fangtao Zhu, Cunwei Cheng.
Writing – review & editing: Kailin Shen, Fangtao Zhu, Cunwei Cheng, Haibin Yu.
Abbreviations:.
Scientific and Technological Funding sources: Project of the Education Department of Henan Province.
The authors have no conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Supplemental Digital Content is available for this article.
How to cite this article: Shen K, Zhu F, Cheng C, Yu H. Exploring the causal relationship between plasma lipids and varicose veins of lower extremity: A comprehensive two-sample Mendelian randomization study. Medicine 2024;103:36(e39514).
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What not to include in your discussion section. Step 1: Summarize your key findings. Step 2: Give your interpretations. Step 3: Discuss the implications. Step 4: Acknowledge the limitations. Step 5: Share your recommendations. Discussion section example. Other interesting articles.
Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and ...
The discussion section is often considered the most important part of your research paper because it: Most effectively demonstrates your ability as a researcher to think critically about an issue, to develop creative solutions to problems based upon a logical synthesis of the findings, and to formulate a deeper, more profound understanding of the research problem under investigation;
This discussion example is from an engineering research paper. The authors are restating their aims first, which is to compare different types of storm-tracking software. Then, they are providing a brief summary of the methods. Here, they are testing different storm-tracking software under different conditions to see which performs the best.
1.Introduction—mention gaps in previous research¹⁻². 2. Summarizing key findings—let your data speak¹⁻². 3. Interpreting results—compare with other papers¹⁻². 4. Addressing limitations—their potential impact on the results¹⁻². 5. Implications for future research—how to explore further¹⁻².
The discussion section is one of the final parts of a research paper, in which an author describes, analyzes, and interprets their findings. They explain the significance of those results and tie everything back to the research question(s). In this handout, you will find a description of what a discussion section does, explanations of how to ...
The discussion section provides an analysis and interpretation of the findings, compares them with previous studies, identifies limitations, and suggests future directions for research. This section combines information from the preceding parts of your paper into a coherent story. By this point, the reader already knows why you did your study ...
Begin the Discussion section by restating your statement of the problem and briefly summarizing the major results. Do not simply repeat your findings. Rather, try to create a concise statement of the main results that directly answer the central research question that you stated in the Introduction section.
Papers usually end with a concluding section, often called the "Discussion.". The Discussion is your opportunity to evaluate and interpret the results of your study or paper, draw inferences and conclusions from it, and communicate its contributions to science and/or society. Use the present tense when writing the Discussion section.
In an empirical research paper, the purpose of the Discussion section is to interpret the results and discuss their implications, thereby establishing (and often qualifying) the practical and scholarly significance of the present study. It may be helpful to think of the Discussion section as the inverse of the introduction to an empirical ...
The discussion section of a research paper is where the author analyzes and explains the importance of the study's results. It presents the conclusions drawn from the study, compares them to previous research, and addresses any potential limitations or weaknesses. The discussion section should also suggest areas for future research.
The examples below are from 72,017 full-text PubMed research papers that I analyzed in order to explore common ways to start writing the Discussion section. Research papers included in this analysis were selected at random from those uploaded to PubMed Central between the years 2016 and 2021. Note that I used the BioC API to download the data ...
Step 1: Restate your research problem and research questions. The first step in writing up your discussion chapter is to remind your reader of your research problem, as well as your research aim (s) and research questions. If you have hypotheses, you can also briefly mention these.
This section is often considered the most important part of a research paper because it most effectively demonstrates your ability as a researcher to think critically about an issue, to develop creative solutions to problems based on the findings, and to formulate a deeper, more profound understanding of the research problem you are studying.. The discussion section is where you explore the ...
Papers that are submitted to a journal for publication are sent out to several scientists (peers) who look carefully at the paper to see if it is "good science". These reviewers then recommend to the editor of a journal whether or not a paper should be published. Most journals have publication guidelines. Ask for them and follow them exactly.
Discussion is mainly the section in a research paper that makes the readers understand the exact meaning of the results achieved in a study by exploring the significant points of the research, its ...
Step 2: Interpret Your Results. In the next step, talk about what your findings really mean. Share why the information you gathered is important. Connect each result to the questions you were trying to answer and the goals you set for your research.
Writing a discussion section is where you really begin to add your interpretations to the work. In this critical part of the research paper, you start the process of explaining any links and correlations apparent in your data. If you left few interesting leads and open questions in the results section, the discussion is simply a matter of ...
The discussion section, a systematic critical appraisal of results, is a key part of a research paper, wherein the authors define, critically examine, describe and interpret their findings ...
Below are helpful tips for writing the results and discussion section of a research paper: Please don't repeat the results in the discussion; start with repeating the research questions and explain how the results answer them. Start from the simple results to the complex; you can even start with the conclusion first, but ensure it is ...
Table of contents. What not to include in your discussion section. Step 1: Summarise your key findings. Step 2: Give your interpretations. Step 3: Discuss the implications. Step 4: Acknowledge the limitations. Step 5: Share your recommendations. Discussion section example.
The discussion section can be written in 3 parts: an introductory paragraph, intermediate paragraphs and a conclusion paragraph. For intermediate paragraphs, a "divide and conquer" approach, meaning a full paragraph describing each of the study endpoints, can be used. In conclusion, academic writing is similar to other skills, and practice ...
A strong Discussion section: Tells the main conclusion of the paper in one or two sentences. Tells how the paper's results contribute to answering the big questions posed in the Introduction. Explains how (and why) this work agrees or disagrees with other, similar work. Explains how the limitations of this study leave the big questions ...
2 .4. Two-sample MR analysis. Two-sample Mendelian randomization analysis was conducted using random-effects inverse-variance weighted (IVW), weighted median, and MR-Egger methods to assess the potential causal relationship between plasma lipids and VVs. Traditional IVW analysis may be susceptible to bias from invalid instruments or pleiotropy.
First, we only focused on the discussion section of RAs. Future cross-disciplinary research on cohesion could examine other RA sections. Second, our study did not explore how the rhetorical moves and steps in the discussion section could affect cohesion. In addition, the data used for this research only included quantitative studies.