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

Frontiers in Endocrinology

Endocrinology

Chaoying Wang¹  Yan Liao¹  Shiqin Zhu¹  Nana Zhang¹  Tong Chen²  Wufan Zhang²  Fan Jia²  Hongyu Zhao²  Yue Yu²  Xinmin Liu² 

[1] Graduate School, Beijing University of Chinese Medicine, Beijing, China;Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China;Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China;

关键词: polycystic ovary syndrome;    25-hydroxyvitamin D;    Mendelian randomization;    obesity;    insulin resistance;    causal inference;    genetic epidemiology;   

DOI  :  10.3389/fendo.2023.1110341

 received in 2022-11-28, accepted in 2023-02-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Liao, Zhao, Chen, Jia, Yu, Zhu, Wang, Zhang and Liu