Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study
BackgroundAccumulating 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 c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1110341/full |
| _version_ | 1811157674251780096 |
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| author | Nana Zhang Nana Zhang Yan Liao Yan Liao Hongyu Zhao Tong Chen Fan Jia Yue Yu Shiqin Zhu Shiqin Zhu Chaoying Wang Chaoying Wang Wufan Zhang Xinmin Liu |
| author_facet | Nana Zhang Nana Zhang Yan Liao Yan Liao Hongyu Zhao Tong Chen Fan Jia Yue Yu Shiqin Zhu Shiqin Zhu Chaoying Wang Chaoying Wang Wufan Zhang Xinmin Liu |
| author_sort | Nana Zhang |
| collection | DOAJ |
| description | BackgroundAccumulating 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.MethodsA 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.ResultsUvMR 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).ConclusionOur 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. |
| first_indexed | 2024-04-10T05:10:15Z |
| format | Article |
| id | doaj.art-2e4a074ffdf645cb8cb57cd91a818107 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T05:10:15Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-2e4a074ffdf645cb8cb57cd91a8181072023-03-09T07:32:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.11103411110341Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization studyNana Zhang0Nana Zhang1Yan Liao2Yan Liao3Hongyu Zhao4Tong Chen5Fan Jia6Yue Yu7Shiqin Zhu8Shiqin Zhu9Chaoying Wang10Chaoying Wang11Wufan Zhang12Xinmin Liu13Graduate School, Beijing University of Chinese Medicine, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBackgroundAccumulating 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.MethodsA 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.ResultsUvMR 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).ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1110341/fullpolycystic ovary syndrome25-hydroxyvitamin DMendelian randomizationobesityinsulin resistancecausal inference |
| spellingShingle | Nana Zhang Nana Zhang Yan Liao Yan Liao Hongyu Zhao Tong Chen Fan Jia Yue Yu Shiqin Zhu Shiqin Zhu Chaoying Wang Chaoying Wang Wufan Zhang Xinmin Liu Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study Frontiers in Endocrinology polycystic ovary syndrome 25-hydroxyvitamin D Mendelian randomization obesity insulin resistance causal inference |
| 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 | polycystic ovary syndrome 25-hydroxyvitamin D Mendelian randomization obesity insulin resistance causal inference |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1110341/full |
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