Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 9:14:1110341.
doi: 10.3389/fendo.2023.1110341. eCollection 2023.

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

Nana Zhang  1   2 , Yan Liao  1   2 , Hongyu Zhao  2 , Tong Chen  2 , Fan Jia  2 , Yue Yu  2 , Shiqin Zhu  1   2 , Chaoying Wang  1   2 , Wufan Zhang  2 , Xinmin Liu  2
Affiliations

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

Nana Zhang et al. Front Endocrinol (Lausanne). .

Abstract

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.

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

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The framework of the bidirectional two-sample Mendelian randomization study between polycystic ovary syndrome and 25-hydroxyvitamin D. SNP, single nucleotide polymorphism; BMI, body mass index; WHR, waist-to-hip ratio; WC, waist circumference; HC, hip circumference; LD, linkage disequilibrium.
Figure 2
Figure 2
The leave-one-out analysis plot (A) Leave-one-out plot for PCOS on 25OHD. (B) Leave-one-out plot for 25OHD on PCOS.
Figure 3
Figure 3
Comparisons of Mendelian randomization results. (A) Comparisons of Mendelian randomization results for PCOS on 25OHD; (B) Comparisons of Mendelian randomization results for 25OHD on PCOS. PCOS, polycystic ovary syndrome; 25OHD, 25-Hydroxyvitamin D; OR, odds ratio; 95% CI, 95% confidence interval; BMI, body mass index; WHR, waist-to-hip ratio; WC, waist circumference; HC, hip circumference.
See this image and copyright information in PMC

References

    1. Belenkaia LV, Lazareva LM, Walker W, Lizneva DV, Suturina LV. Criteria, phenotypes and prevalence of polycystic ovary syndrome. Minerva Ginecol. (2019) 71:211–23. doi: 10.23736/S0026-4784.19.04404-6 - DOI - PubMed
    1. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod (2004) 19:41–7. doi: 10.1093/humrep/deh098 - DOI - PubMed
    1. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med (2010) 8:41. doi: 10.1186/1741-7015-8-41 - DOI - PMC - PubMed
    1. Holick MF. Vitamin d deficiency. N Engl J Med (2007) 357:266–81. doi: 10.1056/NEJMra070553 - DOI - PubMed
    1. Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin d deficiency: A systematic review and meta-analysis. Obes Rev (2015) 16:341–9. doi: 10.1111/obr.12239 - DOI - PubMed

Publication types