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Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study

BACKGROUND: Accumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the cau...

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Autores principales: Zhang, Nana, Liao, Yan, Zhao, Hongyu, Chen, Tong, Jia, Fan, Yu, Yue, Zhu, Shiqin, Wang, Chaoying, Zhang, Wufan, Liu, Xinmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034407/
https://www.ncbi.nlm.nih.gov/pubmed/36967791
http://dx.doi.org/10.3389/fendo.2023.1110341
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author Zhang, Nana
Liao, Yan
Zhao, Hongyu
Chen, Tong
Jia, Fan
Yu, Yue
Zhu, Shiqin
Wang, Chaoying
Zhang, Wufan
Liu, Xinmin
author_facet Zhang, Nana
Liao, Yan
Zhao, Hongyu
Chen, Tong
Jia, Fan
Yu, Yue
Zhu, Shiqin
Wang, Chaoying
Zhang, Wufan
Liu, Xinmin
author_sort Zhang, Nana
collection PubMed
description BACKGROUND: Accumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well. RESULTS: UvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn’t support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280). CONCLUSION: Our findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary.
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spelling pubmed-100344072023-03-24 Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study Zhang, Nana Liao, Yan Zhao, Hongyu Chen, Tong Jia, Fan Yu, Yue Zhu, Shiqin Wang, Chaoying Zhang, Wufan Liu, Xinmin Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Accumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well. RESULTS: UvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn’t support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280). CONCLUSION: Our findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034407/ /pubmed/36967791 http://dx.doi.org/10.3389/fendo.2023.1110341 Text en Copyright © 2023 Zhang, Liao, Zhao, Chen, Jia, Yu, Zhu, Wang, Zhang and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Zhang, Nana
Liao, Yan
Zhao, Hongyu
Chen, Tong
Jia, Fan
Yu, Yue
Zhu, Shiqin
Wang, Chaoying
Zhang, Wufan
Liu, Xinmin
Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title_full Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title_fullStr Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title_full_unstemmed Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title_short Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
title_sort polycystic ovary syndrome and 25-hydroxyvitamin d: a bidirectional two-sample mendelian randomization study
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034407/
https://www.ncbi.nlm.nih.gov/pubmed/36967791
http://dx.doi.org/10.3389/fendo.2023.1110341
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