{"title":"探索炎性细胞因子与椎间盘退变之间的因果关系:孟德尔随机试验","authors":"Tao Xu, Guangzi Chen, Jian Li, Yingchi Zhang","doi":"10.1002/jsp2.1349","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD.</p>\n </section>\n \n <section>\n \n <h3> Method</h3>\n \n <p>We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results.</p>\n </section>\n \n <section>\n \n <h3> Result</h3>\n \n <p>We found interferon-gamma (IFN-γ, <i>p</i> = 2.14 × 10–6, OR = 0.870, 95% CI = 0.821–0.921), interleukin-1 beta (IL-1b, <i>p</i> = 0.012, OR = 0.951, 95% CI = 0.914–0.989), interleukin-4 (IL-4, <i>p</i> = 0.034, OR = 0.946, 95% CI = 0.899–0.996), interleukin-18 (IL-18, <i>p</i> = 0.028, OR = 0.964, 95% CI = 0.934–0.996), granulocyte colony-stimulating factor (GCSF, <i>p</i> = 0.010, OR = 0.919, 95% CI = 0.861–0.980), and Stromal cell-derived factor 1a (SDF1a, <i>p</i> = 0.014, OR = 1.072, 95% CI = 1.014–1.134) were causally associated with risk of IVDD.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237178/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: A Mendelian randomization\",\"authors\":\"Tao Xu, Guangzi Chen, Jian Li, Yingchi Zhang\",\"doi\":\"10.1002/jsp2.1349\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Method</h3>\\n \\n <p>We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Result</h3>\\n \\n <p>We found interferon-gamma (IFN-γ, <i>p</i> = 2.14 × 10–6, OR = 0.870, 95% CI = 0.821–0.921), interleukin-1 beta (IL-1b, <i>p</i> = 0.012, OR = 0.951, 95% CI = 0.914–0.989), interleukin-4 (IL-4, <i>p</i> = 0.034, OR = 0.946, 95% CI = 0.899–0.996), interleukin-18 (IL-18, <i>p</i> = 0.028, OR = 0.964, 95% CI = 0.934–0.996), granulocyte colony-stimulating factor (GCSF, <i>p</i> = 0.010, OR = 0.919, 95% CI = 0.861–0.980), and Stromal cell-derived factor 1a (SDF1a, <i>p</i> = 0.014, OR = 1.072, 95% CI = 1.014–1.134) were causally associated with risk of IVDD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.</p>\\n </section>\\n </div>\",\"PeriodicalId\":14876,\"journal\":{\"name\":\"JOR Spine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237178/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JOR Spine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1349\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOR Spine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1349","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
引用次数: 0
摘要
背景:以前的一些研究报告称,炎性细胞因子与椎间盘退变(IVDD)有关。然而,炎性细胞因子与 IVDD 之间的因果关系仍不明确。本研究采用孟德尔随机法(MR)分析炎性细胞因子与 IVDD 风险之间的因果关系:我们使用了对8293名芬兰人进行的全基因组关联研究(GWAS)荟萃分析中与炎性细胞因子相关的基因变异作为工具变量,IVDD数据来自FinnGen联盟。主要分析方法是利用带有随机效应的逆方差加权法(IVW)来评估因果关系。此外,还采用了 MR-Egger、加权中位数、简单模式、加权模式、MR 多变量残差和离群值等补充方法,以增强最终结果的稳健性:我们发现干扰素-γ(IFN-γ,p = 2.14 × 10-6,OR = 0.870,95% CI = 0.821-0.921)、白细胞介素-1 beta(IL-1b,p = 0.012,OR = 0.951,95% CI = 0.914-0.989)、白细胞介素-4(IL-4,p = 0.034,OR = 0.946,95% CI = 0.899-0.996)、白细胞介素-18(IL-18,p = 0.028,OR = 0.964,95% CI = 0.934-0.996)、粒细胞集落刺激因子(GCSF,p = 0.010,OR = 0.919,95% CI = 0.861-0.980)和基质细胞衍生因子 1a(SDF1a,p = 0.014,OR = 1.072,95% CI = 1.014-1.134)与 IVDD 风险存在因果关系:我们的磁共振分析发现,六种炎症细胞因子(IFN-γ、IL-1b、IL-4、IL-18、SDF1a 和 GCSF)与 IVDD 风险改变之间存在潜在的因果关系。
Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: A Mendelian randomization
Background
Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD.
Method
We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results.
Result
We found interferon-gamma (IFN-γ, p = 2.14 × 10–6, OR = 0.870, 95% CI = 0.821–0.921), interleukin-1 beta (IL-1b, p = 0.012, OR = 0.951, 95% CI = 0.914–0.989), interleukin-4 (IL-4, p = 0.034, OR = 0.946, 95% CI = 0.899–0.996), interleukin-18 (IL-18, p = 0.028, OR = 0.964, 95% CI = 0.934–0.996), granulocyte colony-stimulating factor (GCSF, p = 0.010, OR = 0.919, 95% CI = 0.861–0.980), and Stromal cell-derived factor 1a (SDF1a, p = 0.014, OR = 1.072, 95% CI = 1.014–1.134) were causally associated with risk of IVDD.
Conclusion
Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.