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The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis

Background: Although observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blo...

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Autores principales: Zhu, Xiaoqi, Hong, Xiang, Wu, Jingying, Zhao, Fanqi, Wang, Wei, Huang, Lingling, Li, Jiuming, Wang, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384410/
https://www.ncbi.nlm.nih.gov/pubmed/37513548
http://dx.doi.org/10.3390/nu15143130
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author Zhu, Xiaoqi
Hong, Xiang
Wu, Jingying
Zhao, Fanqi
Wang, Wei
Huang, Lingling
Li, Jiuming
Wang, Bei
author_facet Zhu, Xiaoqi
Hong, Xiang
Wu, Jingying
Zhao, Fanqi
Wang, Wei
Huang, Lingling
Li, Jiuming
Wang, Bei
author_sort Zhu, Xiaoqi
collection PubMed
description Background: Although observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blood lipids and female infertility. Methods: Single-nucleotide polymorphisms associated with lipid traits in univariate analysis were obtained from the Million Veteran Program (MVP) and Global Lipids Genetics Consortium (GLGC), involving up to 215,551 and 188,577 European individuals, respectively. Blood lipids in multivariate analysis were obtained from the latest genome-wide association study meta-analysis with lipid levels in 73 studies encompassing >300,000 participants. Data on female infertility were obtained from the FinnGen Consortium R6 release, which included 6481 samples and 75,450 controls. Subsequently, MR analysis was performed using inverse variance-weighted (IVW), weighted median, weighted-mode, simple-mode and MR-Egger regression to demonstrate the causal relationship between lipids and female infertility. Results: After controlling confounding factors including body mass index and age at menarche, two-sample MR demonstrated that genetically predicted LDL-C and TC were causally associated with the risk of female infertility (When the genetic instruments come from the MVP database, LDL-C and female infertility, IVW OR: 1.13, 95% CI: 1.001–1.269, p = 0.047; TC and female infertility, IVW OR: 1.16, 95% CI: 1.018–1.317, p = 0.025, and when the genetic instruments came from the GLGC database, LDL-C and female infertility, IVW OR: 1.10, 95% CI: 1.008–1.210, p = 0.033; TC and female infertility, IVW OR: 1.14, 95% CI: 1.024–1.258, p = 0.015). However, the IVW estimate showed that HDL-C was not significantly associated with the risk of female infertility (when the genetic instruments came from the MVP database, IVW OR: 1.00, 95% CI: 0.887–1.128, p = 0.999; when the genetic instruments came from the GLGC database, IVW OR: 1.00, 95% CI: 0.896–1.111, p = 0.968). The multivariable MR analysis also provided evidence that LDL-C (OR: 1.12, 95% CI: 1.006–1.243, p = 0.042) was significantly associated with the risk of female infertility after considering the correlation of all lipid-related traits. Conclusion: These findings support a causal relationship between increased LDL-cholesterol and increased female infertility risk. Furthermore, the association between lipid-related traits and female infertility risk merits more studies.
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spelling pubmed-103844102023-07-30 The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis Zhu, Xiaoqi Hong, Xiang Wu, Jingying Zhao, Fanqi Wang, Wei Huang, Lingling Li, Jiuming Wang, Bei Nutrients Article Background: Although observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blood lipids and female infertility. Methods: Single-nucleotide polymorphisms associated with lipid traits in univariate analysis were obtained from the Million Veteran Program (MVP) and Global Lipids Genetics Consortium (GLGC), involving up to 215,551 and 188,577 European individuals, respectively. Blood lipids in multivariate analysis were obtained from the latest genome-wide association study meta-analysis with lipid levels in 73 studies encompassing >300,000 participants. Data on female infertility were obtained from the FinnGen Consortium R6 release, which included 6481 samples and 75,450 controls. Subsequently, MR analysis was performed using inverse variance-weighted (IVW), weighted median, weighted-mode, simple-mode and MR-Egger regression to demonstrate the causal relationship between lipids and female infertility. Results: After controlling confounding factors including body mass index and age at menarche, two-sample MR demonstrated that genetically predicted LDL-C and TC were causally associated with the risk of female infertility (When the genetic instruments come from the MVP database, LDL-C and female infertility, IVW OR: 1.13, 95% CI: 1.001–1.269, p = 0.047; TC and female infertility, IVW OR: 1.16, 95% CI: 1.018–1.317, p = 0.025, and when the genetic instruments came from the GLGC database, LDL-C and female infertility, IVW OR: 1.10, 95% CI: 1.008–1.210, p = 0.033; TC and female infertility, IVW OR: 1.14, 95% CI: 1.024–1.258, p = 0.015). However, the IVW estimate showed that HDL-C was not significantly associated with the risk of female infertility (when the genetic instruments came from the MVP database, IVW OR: 1.00, 95% CI: 0.887–1.128, p = 0.999; when the genetic instruments came from the GLGC database, IVW OR: 1.00, 95% CI: 0.896–1.111, p = 0.968). The multivariable MR analysis also provided evidence that LDL-C (OR: 1.12, 95% CI: 1.006–1.243, p = 0.042) was significantly associated with the risk of female infertility after considering the correlation of all lipid-related traits. Conclusion: These findings support a causal relationship between increased LDL-cholesterol and increased female infertility risk. Furthermore, the association between lipid-related traits and female infertility risk merits more studies. MDPI 2023-07-13 /pmc/articles/PMC10384410/ /pubmed/37513548 http://dx.doi.org/10.3390/nu15143130 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhu, Xiaoqi
Hong, Xiang
Wu, Jingying
Zhao, Fanqi
Wang, Wei
Huang, Lingling
Li, Jiuming
Wang, Bei
The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title_full The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title_fullStr The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title_full_unstemmed The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title_short The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis
title_sort association between circulating lipids and female infertility risk: a univariable and multivariable mendelian randomization analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384410/
https://www.ncbi.nlm.nih.gov/pubmed/37513548
http://dx.doi.org/10.3390/nu15143130
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