The causal association between systemic inflammatory regulators and primary ovarian insufficiency: a bidirectional mendelian randomization study.
Causal inference
Mendelian randomization study
Primary ovarian insufficiency
Systemic inflammatory regulators
Journal
Journal of ovarian research
ISSN: 1757-2215
Titre abrégé: J Ovarian Res
Pays: England
ID NLM: 101474849
Informations de publication
Date de publication:
14 Sep 2023
14 Sep 2023
Historique:
received:
14
04
2023
accepted:
03
09
2023
medline:
18
9
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
epublish
Résumé
Recent studies have suggested a potential link between systemic inflammatory regulators and primary ovarian insufficiency (POI); however, a causal relationship between them remains unclear. In this study, we explored the causal link between systemic inflammatory regulators and POI risk using a bidirectional, two-sample Mendelian randomization (MR) strategy. This approach utilized the most extensive genome-wide association study involving 41 systemic inflammatory regulators in a sample of 8,293 Finnish individuals and POI data from the FinnGen consortium (254 cases vs. 118,228 controls). The inverse variance weighting approach served as a primary MR method, and four additional MR techniques (Maximum Likelihood, MR-Egger, Weighted Median, and constrained maximum likelihood and model averaging Bayesian information criterion ) were applied to support and validate results. Cochran's Q statistics were used to assess the heterogeneity of instrumental variables, whereas the MR-Egger and MR Pleiotropy Residual Sum and Outlier tests detected horizontal pleiotropy. The MR Steiger test evaluated the strength of a causal association. Our findings suggest that lower levels of vascular endothelial growth factor (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.54-0.99, P = 0.046) and interleukin-10 (OR = 0.54, 95% CI: 0.33-0.85, P = 0.021) are associated with an increased risk of POI. Reverse MR analysis revealed no significant effect of POI on the expression of these 41 systemic inflammatory regulators. No notable heterogeneity or horizontal pleiotropy was observed in the instrumental variables. This study revealed a causal association between 41 systemic inflammatory regulators and POI, demonstrating that decreased levels of VEGF and IL-10 are linked to an elevated risk of POI. Further investigations are necessary to assess the potential of these biomarkers as early predictors, preventive strategies, and therapeutic targets for POI.
Sections du résumé
BACKGROUND
BACKGROUND
Recent studies have suggested a potential link between systemic inflammatory regulators and primary ovarian insufficiency (POI); however, a causal relationship between them remains unclear. In this study, we explored the causal link between systemic inflammatory regulators and POI risk using a bidirectional, two-sample Mendelian randomization (MR) strategy.
RESULTS
RESULTS
This approach utilized the most extensive genome-wide association study involving 41 systemic inflammatory regulators in a sample of 8,293 Finnish individuals and POI data from the FinnGen consortium (254 cases vs. 118,228 controls). The inverse variance weighting approach served as a primary MR method, and four additional MR techniques (Maximum Likelihood, MR-Egger, Weighted Median, and constrained maximum likelihood and model averaging Bayesian information criterion ) were applied to support and validate results. Cochran's Q statistics were used to assess the heterogeneity of instrumental variables, whereas the MR-Egger and MR Pleiotropy Residual Sum and Outlier tests detected horizontal pleiotropy. The MR Steiger test evaluated the strength of a causal association. Our findings suggest that lower levels of vascular endothelial growth factor (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.54-0.99, P = 0.046) and interleukin-10 (OR = 0.54, 95% CI: 0.33-0.85, P = 0.021) are associated with an increased risk of POI. Reverse MR analysis revealed no significant effect of POI on the expression of these 41 systemic inflammatory regulators. No notable heterogeneity or horizontal pleiotropy was observed in the instrumental variables.
CONCLUSIONS
CONCLUSIONS
This study revealed a causal association between 41 systemic inflammatory regulators and POI, demonstrating that decreased levels of VEGF and IL-10 are linked to an elevated risk of POI. Further investigations are necessary to assess the potential of these biomarkers as early predictors, preventive strategies, and therapeutic targets for POI.
Identifiants
pubmed: 37710281
doi: 10.1186/s13048-023-01272-5
pii: 10.1186/s13048-023-01272-5
pmc: PMC10502980
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
191Subventions
Organisme : Self-select Fund of Zhongda Hospital
ID : ZDYYZXKT2019001
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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