Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study

Background Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.Method Genome-wide association study (GWAS) data of GM was obtained from t...

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Main Authors: Tiefeng Cao, Yunfei Wang, Shen Huimin
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Obstetrics and Gynaecology
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Online Access:https://www.tandfonline.com/doi/10.1080/01443615.2024.2362415
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author Tiefeng Cao
Yunfei Wang
Shen Huimin
author_facet Tiefeng Cao
Yunfei Wang
Shen Huimin
author_sort Tiefeng Cao
collection DOAJ
description Background Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.Method Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran’s Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.Result A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.Conclusions This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
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spelling doaj-art-5f64795bb68c48c988388c234acb4b602025-01-09T12:13:17ZengTaylor & Francis GroupJournal of Obstetrics and Gynaecology0144-36151364-68932024-12-0144110.1080/01443615.2024.2362415Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation studyTiefeng Cao0Yunfei Wang1Shen Huimin2Department of Gynaecology, First Affiliated Hospital of Sun Yat­Sen University, Guangzhou, P.R. ChinaDepartment of Oncology, First Affiliated Hospital of Sun Yat­Sen University, Guangzhou, P.R. ChinaDepartment of Gynaecology, First Affiliated Hospital of Sun Yat­Sen University, Guangzhou, P.R. ChinaBackground Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.Method Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran’s Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.Result A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.Conclusions This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.https://www.tandfonline.com/doi/10.1080/01443615.2024.2362415Gut microbiotaendometriosisMendelian randomisation
spellingShingle Tiefeng Cao
Yunfei Wang
Shen Huimin
Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
Journal of Obstetrics and Gynaecology
Gut microbiota
endometriosis
Mendelian randomisation
title Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
title_full Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
title_fullStr Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
title_full_unstemmed Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
title_short Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study
title_sort causal effects between gut microbiota and endometriosis a two sample mendelian randomisation study
topic Gut microbiota
endometriosis
Mendelian randomisation
url https://www.tandfonline.com/doi/10.1080/01443615.2024.2362415
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