Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study
Abstract Background Current evidence suggests a significant association between metabolites and ovarian cancer (OC); however, the causal relationship between the two remains unclear. This study employs Mendelian randomization (MR) to investigate the causal effects between different metabolites and O...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-024-09997-3 |
| _version_ | 1827369985496842240 |
|---|---|
| author | Yedong Huang Wenyu Lin Xiangqin Zheng |
| author_facet | Yedong Huang Wenyu Lin Xiangqin Zheng |
| author_sort | Yedong Huang |
| collection | DOAJ |
| description | Abstract Background Current evidence suggests a significant association between metabolites and ovarian cancer (OC); however, the causal relationship between the two remains unclear. This study employs Mendelian randomization (MR) to investigate the causal effects between different metabolites and OC. Methods In this study, a total of 637 metabolites were selected as the exposure variables from the Genome-wide Association Study (GWAS) database ( http://gwas.mrcieu.ac.uk/datasets/ ). The OC related GWAS dataset (ieu-b-4963) was chosen as the outcome variable. R software and the TwoSampleMR package were utilized for the analysis in this study. MR analysis employed the inverse variance-weighted method (IVW), MR-Egger and weighted median (WM) for regression fitting, taking into consideration potential biases caused by linkage disequilibrium and weak instrument variables. Metabolites that did not pass the tests for heterogeneity and horizontal pleiotropy were considered to have no significant causal effect on the outcome. Steiger’s upstream test was used to determine the causal direction between the exposure and outcome variables. Results The results from IVW analysis revealed that a total of 31 human metabolites showed a significant causal effect on OC (P < 0.05). Among them, 9 metabolites exhibited consistent and stable causal effects, which were confirmed by Steiger’s upstream test (P < 0.05). Among these 9 metabolites, Androsterone sulfate, Propionylcarnitine, 5alpha-androstan-3beta,17beta-diol disulfate, Total lipids in medium VLDL and Concentration of medium VLDL particles demonstrated a significant positive causal effect on OC, indicating that these metabolites promote the occurrence of OC. On the other hand, X-12,093, Octanoylcarnitine, N2,N2-dimethylguanosine, and Cis-4-decenoyl carnitine showed a significant negative causal association with OC, suggesting that these metabolites can inhibit the occurrence of OC. Conclusions The study revealed the complex effect of metabolites on OC through Mendelian randomization. As promising biomarkers, these metabolites are worthy of further clinical validation. |
| first_indexed | 2024-03-08T10:00:41Z |
| format | Article |
| id | doaj.art-4496a726436e4558b00f323b742bef9c |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-08T10:00:41Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-4496a726436e4558b00f323b742bef9c2024-01-29T10:59:57ZengBMCBMC Genomics1471-21642024-01-012511910.1186/s12864-024-09997-3Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization studyYedong Huang0Wenyu Lin1Xiangqin Zheng2College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityCollege of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityCollege of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityAbstract Background Current evidence suggests a significant association between metabolites and ovarian cancer (OC); however, the causal relationship between the two remains unclear. This study employs Mendelian randomization (MR) to investigate the causal effects between different metabolites and OC. Methods In this study, a total of 637 metabolites were selected as the exposure variables from the Genome-wide Association Study (GWAS) database ( http://gwas.mrcieu.ac.uk/datasets/ ). The OC related GWAS dataset (ieu-b-4963) was chosen as the outcome variable. R software and the TwoSampleMR package were utilized for the analysis in this study. MR analysis employed the inverse variance-weighted method (IVW), MR-Egger and weighted median (WM) for regression fitting, taking into consideration potential biases caused by linkage disequilibrium and weak instrument variables. Metabolites that did not pass the tests for heterogeneity and horizontal pleiotropy were considered to have no significant causal effect on the outcome. Steiger’s upstream test was used to determine the causal direction between the exposure and outcome variables. Results The results from IVW analysis revealed that a total of 31 human metabolites showed a significant causal effect on OC (P < 0.05). Among them, 9 metabolites exhibited consistent and stable causal effects, which were confirmed by Steiger’s upstream test (P < 0.05). Among these 9 metabolites, Androsterone sulfate, Propionylcarnitine, 5alpha-androstan-3beta,17beta-diol disulfate, Total lipids in medium VLDL and Concentration of medium VLDL particles demonstrated a significant positive causal effect on OC, indicating that these metabolites promote the occurrence of OC. On the other hand, X-12,093, Octanoylcarnitine, N2,N2-dimethylguanosine, and Cis-4-decenoyl carnitine showed a significant negative causal association with OC, suggesting that these metabolites can inhibit the occurrence of OC. Conclusions The study revealed the complex effect of metabolites on OC through Mendelian randomization. As promising biomarkers, these metabolites are worthy of further clinical validation.https://doi.org/10.1186/s12864-024-09997-3Mendelian randomizationOvarian cancerMetabolitesCasual effect |
| spellingShingle | Yedong Huang Wenyu Lin Xiangqin Zheng Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study BMC Genomics Mendelian randomization Ovarian cancer Metabolites Casual effect |
| title | Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study |
| title_full | Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study |
| title_fullStr | Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study |
| title_full_unstemmed | Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study |
| title_short | Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study |
| title_sort | causal association between 637 human metabolites and ovarian cancer a mendelian randomization study |
| topic | Mendelian randomization Ovarian cancer Metabolites Casual effect |
| url | https://doi.org/10.1186/s12864-024-09997-3 |
| work_keys_str_mv | AT yedonghuang causalassociationbetween637humanmetabolitesandovariancanceramendelianrandomizationstudy AT wenyulin causalassociationbetween637humanmetabolitesandovariancanceramendelianrandomizationstudy AT xiangqinzheng causalassociationbetween637humanmetabolitesandovariancanceramendelianrandomizationstudy |