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

Abstract

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.

1,25-dihydroxyvitamin D3 alleviates bisphenol A-induced apoptosis in KGN cells by improving mitochondrial activity and blocking the mitochondrial cytochrome c apoptotic pathway

“…Recently, BPA has been demonstrated to impair reproductive function and is potentially involved in PCOS development. In addition, vitamin D de ciency may be involved in PCOS pathogenesis [19]. Ovulatory function improves in some patients after vitamin D supplementation; however, the exact mechanism is unclear.…”

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study

“…The formula is provided where R 2 represents the proportion of variance explained by the SNP, EAF represents the effect allele frequency of the SNP, β represents the effect size of the SNP, and n represents the sample size of the GWAS. An F -statistic <10 indicates potential weak instrument bias and excludes corresponding SNPs ( Chen et al , 2019 ; Zhang et al , 2023b ). …”

“…The random-effect inverse-variance weighted (IVW) method was regarded as the primary analysis ( Burgess et al , 2019 ), and MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods ( Zhang et al , 2023b ). MR-Egger intercept analysis and MR-PRESSO were employed to test horizontal pleiotropy and then outlier SNPs reflecting pleiotropic biases ( Bowden et al , 2015 ; Verbanck et al , 2018 ).…”

Genetically predicted 15 circulating blood cell traits and Esophageal Cancer：a comprehensive Mendelian randomization study

“…Mendelian randomization (MR) utilizes single-nucleotide polymorphisms (SNPs) as instrumental variables to determine potential causal relationships between exposure and outcome by minimizing the impact of confounding factors and nonmeasurement errors [11]. By adhering to Mendelian inheritance laws, MR can help avoid issues such as reverse causality [12]. Consequently, This study sought to investigate the causal link between circulating blood cell traits and EC through a thorough two-sample bidirectional MR analysis.…”