{"title":"血浆代谢物与腕管综合征风险之间的因果关系：泯灭随机研究的证据。","authors":"Wenbao Wu, Daofeng Fan, Chong Zheng, Binfu Que, Qing Qing Lian, Yangui Chen, Rui Qiu","doi":"10.3389/fmolb.2024.1431329","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Carpal tunnel syndrome (CTS) is a common symptom of nerve compression and a leading cause of pain and hand dysfunction. However, the underlying biological mechanisms are not fully understood. The aim of this study was to reveal the causal effect of circulating metabolites on susceptibility to CTS.</p><p><strong>Methods: </strong>We employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Model, to examine the association between 1,400 metabolites and the risk of developing CTS. We obtained Single-nucleotide polymorphisms (SNPs) associated with 1,400 metabolites from the Canadian Longitudinal Study on Aging (CLSA) cohort. CTS data was derived from the FinnGen consortium, which included 11,208 cases and 1,95,047 controls of European ancestry.</p><p><strong>Results: </strong>The results of the two-sample MR study indicated an association between 77 metabolites (metabolite ratios) and CTS. After false discovery rate (FDR) correction, a strong causal association between glucuronate levels (odd ratio (OR) [95% CI]: 0.98 [0.97-0.99], p <sub>FDR</sub> = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p <sub>FDR</sub> = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p <sub>FDR</sub> = 0.047) and CTS was finally identified.</p><p><strong>Conclusion: </strong>In summary, the results of this study suggest that the identified glucuronate, the ratio of AMP to phosphate, and cysteinylglycine disulfide levels can be considered as metabolic biomarkers for CTS screening and prevention in future clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1431329"},"PeriodicalIF":3.9000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484071/pdf/","citationCount":"0","resultStr":"{\"title\":\"Causal relationship between plasma metabolites and carpal tunnel syndrome risk: evidence from a mendelian randomization study.\",\"authors\":\"Wenbao Wu, Daofeng Fan, Chong Zheng, Binfu Que, Qing Qing Lian, Yangui Chen, Rui Qiu\",\"doi\":\"10.3389/fmolb.2024.1431329\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Carpal tunnel syndrome (CTS) is a common symptom of nerve compression and a leading cause of pain and hand dysfunction. However, the underlying biological mechanisms are not fully understood. The aim of this study was to reveal the causal effect of circulating metabolites on susceptibility to CTS.</p><p><strong>Methods: </strong>We employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Model, to examine the association between 1,400 metabolites and the risk of developing CTS. We obtained Single-nucleotide polymorphisms (SNPs) associated with 1,400 metabolites from the Canadian Longitudinal Study on Aging (CLSA) cohort. CTS data was derived from the FinnGen consortium, which included 11,208 cases and 1,95,047 controls of European ancestry.</p><p><strong>Results: </strong>The results of the two-sample MR study indicated an association between 77 metabolites (metabolite ratios) and CTS. After false discovery rate (FDR) correction, a strong causal association between glucuronate levels (odd ratio (OR) [95% CI]: 0.98 [0.97-0.99], p <sub>FDR</sub> = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p <sub>FDR</sub> = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p <sub>FDR</sub> = 0.047) and CTS was finally identified.</p><p><strong>Conclusion: </strong>In summary, the results of this study suggest that the identified glucuronate, the ratio of AMP to phosphate, and cysteinylglycine disulfide levels can be considered as metabolic biomarkers for CTS screening and prevention in future clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.</p>\",\"PeriodicalId\":12465,\"journal\":{\"name\":\"Frontiers in Molecular Biosciences\",\"volume\":\"11 \",\"pages\":\"1431329\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484071/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Biosciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fmolb.2024.1431329\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2024.1431329","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Causal relationship between plasma metabolites and carpal tunnel syndrome risk: evidence from a mendelian randomization study.
Background: Carpal tunnel syndrome (CTS) is a common symptom of nerve compression and a leading cause of pain and hand dysfunction. However, the underlying biological mechanisms are not fully understood. The aim of this study was to reveal the causal effect of circulating metabolites on susceptibility to CTS.
Methods: We employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Model, to examine the association between 1,400 metabolites and the risk of developing CTS. We obtained Single-nucleotide polymorphisms (SNPs) associated with 1,400 metabolites from the Canadian Longitudinal Study on Aging (CLSA) cohort. CTS data was derived from the FinnGen consortium, which included 11,208 cases and 1,95,047 controls of European ancestry.
Results: The results of the two-sample MR study indicated an association between 77 metabolites (metabolite ratios) and CTS. After false discovery rate (FDR) correction, a strong causal association between glucuronate levels (odd ratio (OR) [95% CI]: 0.98 [0.97-0.99], p FDR = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p FDR = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p FDR = 0.047) and CTS was finally identified.
Conclusion: In summary, the results of this study suggest that the identified glucuronate, the ratio of AMP to phosphate, and cysteinylglycine disulfide levels can be considered as metabolic biomarkers for CTS screening and prevention in future clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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