Lin Sun, Kai-Qing Yan, Qi Zhang, Ji Ma, Bo Shi, Xi-Yuan Yang, Li-Jun Li
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The genetic associations of the variants with IDD were investigated in the largest genome-wide association study from GWAS pipeline using Phesant derived variables from UKBiobank (1045 cases; 461 965 controls). We used a two-sample MR method to evaluate the causal relationship between these five MMPs and IDD. The causal effects were examined by inverse variance weighted (IVW) test. And sensitivity analysis was performed using Q test of IVW and MR-Egger, MR-Egger-intercept and MR-PRESSO.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We found a significant correlation between increased the plasma level of MMP3 and an increased risk of IDD (IVW: OR 1.000564, 95% CI 1.0000304–1.00110; <i>p</i> = 0.0383). The heterogeneity test (MR-Egger Q test: <i>p</i> = 0.346 and IVW Q test: <i>p</i> = 0.460) indicated that there was no heterogeneity in this instrumental variable on the surface. Also, no directional horizontal pleiotropy was observed in the MR analysis (MR-Egger, <i>p</i> = 0.708 and MR-PRESSO, <i>p</i> = 0.609). There was no significant correlation between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our MR analysis found that there is a potential causal relationship between increased the plasma level of MMP3 and the risk of IDD in the European population. There is no potential causal relationship between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705520/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the Causal Relationship Between the Plasma Levels of MMP1 (Matrix Metalloproteinase-1), MMP3, MMP7, MMP10, and MMP12 and Intervertebral Disc Degeneration: Mendelian Randomization\",\"authors\":\"Lin Sun, Kai-Qing Yan, Qi Zhang, Ji Ma, Bo Shi, Xi-Yuan Yang, Li-Jun Li\",\"doi\":\"10.1002/jsp2.70034\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Several matrix metalloproteinases (MMPs) have been reported to be associated with intervertebral disc degeneration (IDD) in several previous studies. However, the causal relationship between MMPs and IDD remains unclear. In this study, Mendelian randomization (MR) was used to analyze the causal relationship between the plasma levels of multiple MMPs and the risk of IDD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The GWAS data of the plasma levels of MMP1, MMP3, MMP7, MMP10, and MMP12 were derived from the genome-wide variation associations of 21 758 European individuals. The genetic associations of the variants with IDD were investigated in the largest genome-wide association study from GWAS pipeline using Phesant derived variables from UKBiobank (1045 cases; 461 965 controls). We used a two-sample MR method to evaluate the causal relationship between these five MMPs and IDD. The causal effects were examined by inverse variance weighted (IVW) test. And sensitivity analysis was performed using Q test of IVW and MR-Egger, MR-Egger-intercept and MR-PRESSO.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We found a significant correlation between increased the plasma level of MMP3 and an increased risk of IDD (IVW: OR 1.000564, 95% CI 1.0000304–1.00110; <i>p</i> = 0.0383). The heterogeneity test (MR-Egger Q test: <i>p</i> = 0.346 and IVW Q test: <i>p</i> = 0.460) indicated that there was no heterogeneity in this instrumental variable on the surface. Also, no directional horizontal pleiotropy was observed in the MR analysis (MR-Egger, <i>p</i> = 0.708 and MR-PRESSO, <i>p</i> = 0.609). 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引用次数: 0
摘要
背景：在之前的几项研究中，已经报道了几种基质金属蛋白酶（MMPs）与椎间盘退变（IDD）有关。然而，MMPs和IDD之间的因果关系尚不清楚。本研究采用孟德尔随机化（Mendelian randomization， MR）方法分析血浆中多种MMPs水平与IDD风险之间的因果关系。方法：从21758名欧洲人的全基因组变异关联中获取血浆中MMP1、MMP3、MMP7、MMP10和MMP12水平的GWAS数据。使用来自UKBiobank的Phesant衍生变量，在GWAS管道中进行了最大的全基因组关联研究，研究了这些变异与IDD的遗传关联(1045例；461 965对照)。我们使用双样本MR方法来评估这五种MMPs与IDD之间的因果关系。采用逆方差加权（IVW）检验因果关系。采用IVW与MR-Egger、mr - egg -intercept、MR-PRESSO的Q检验进行敏感性分析。结果：我们发现血浆中MMP3水平升高与IDD风险增加之间存在显著相关性(IVW: OR 1.000564, 95% CI 1.0000304-1.00110；p = 0.0383)。异质性检验（MR-Egger Q检验：p = 0.346， IVW Q检验：p = 0.460）表明，表面上该工具变量不存在异质性。此外，MR分析中未观察到定向水平多效性（MR- egger, p = 0.708, MR- presso, p = 0.609）。血浆中MMP1、MMP7、MMP10和MMP12水平与IDD风险增加之间无显著相关性。结论：我们的MR分析发现，在欧洲人群中，血浆中MMP3水平升高与IDD风险之间存在潜在的因果关系。血浆中MMP1、MMP7、MMP10和MMP12水平与IDD风险增加之间没有潜在的因果关系。
Exploring the Causal Relationship Between the Plasma Levels of MMP1 (Matrix Metalloproteinase-1), MMP3, MMP7, MMP10, and MMP12 and Intervertebral Disc Degeneration: Mendelian Randomization
Background
Several matrix metalloproteinases (MMPs) have been reported to be associated with intervertebral disc degeneration (IDD) in several previous studies. However, the causal relationship between MMPs and IDD remains unclear. In this study, Mendelian randomization (MR) was used to analyze the causal relationship between the plasma levels of multiple MMPs and the risk of IDD.
Methods
The GWAS data of the plasma levels of MMP1, MMP3, MMP7, MMP10, and MMP12 were derived from the genome-wide variation associations of 21 758 European individuals. The genetic associations of the variants with IDD were investigated in the largest genome-wide association study from GWAS pipeline using Phesant derived variables from UKBiobank (1045 cases; 461 965 controls). We used a two-sample MR method to evaluate the causal relationship between these five MMPs and IDD. The causal effects were examined by inverse variance weighted (IVW) test. And sensitivity analysis was performed using Q test of IVW and MR-Egger, MR-Egger-intercept and MR-PRESSO.
Results
We found a significant correlation between increased the plasma level of MMP3 and an increased risk of IDD (IVW: OR 1.000564, 95% CI 1.0000304–1.00110; p = 0.0383). The heterogeneity test (MR-Egger Q test: p = 0.346 and IVW Q test: p = 0.460) indicated that there was no heterogeneity in this instrumental variable on the surface. Also, no directional horizontal pleiotropy was observed in the MR analysis (MR-Egger, p = 0.708 and MR-PRESSO, p = 0.609). There was no significant correlation between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.
Conclusion
Our MR analysis found that there is a potential causal relationship between increased the plasma level of MMP3 and the risk of IDD in the European population. There is no potential causal relationship between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.
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