Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study

Abstract

Background Polycystic ovary syndrome (PCOS) is often accompanied by increased oxidative stress levels; however, it is still unclear whether PCOS itself is causally related to oxidative stress (OS), whether OS can increase the occurrence of PCOS, and which characteristics of PCOS increase OS levels. Therefore, this study explored the causal relationship between PCOS, its characteristics, and OS. Methods Two-sample bidirectional and two-sample Mendelian randomisation studies were performed based on publicly available statistics from genome-wide association studies. PCOS; its characteristics, such as testosterone, low-density lipoprotein, high-density lipoprotein; and 11 major OS markers (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, catalase, uric acid, zinc, tocopherol, ascorbic acid, retinol, albumin, and total bilirubin), were studied. The main analytical method used was inverse variance weighting (IVW). Pleiotropy was evaluated using the Mendelian randomisation-Egger intercept. Q and P values were used to assess heterogeneity. Results There was no causal relationship between PCOS and the OS indices (all P > 0.05). There was a causal relationship between the OS index, ascorbate level, and PCOS (IVW, odds ratio: 2.112, 95% confidence interval: 1.257–3.549, P = 0.005). In addition, there was a causal relationship between testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, age at menarche, and most OS indices according to the IVW method. The F statistics showed that there was no weak instrumental variable. A sensitivity analysis was performed using the leave-one-out method. No pleiotropy was observed. The results were robust, and the conclusions were reliable. Conclusions This study showed for the first time that there was no causal relationship between PCOS and OS. However, there was a causal relationship between the OS index, ascorbate level, and PCOS. It revealed that PCOS itself could not increase OS, and the increase in OS in PCOS was related to other potential factors, such as testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, and age at menarche.

Using clustering of genetic variants in Mendelian randomization to interrogate the causal pathways underlying multimorbidity

“…We select 11 OS biomarkers from diverse categories. First, as endogenous antioxidants are highly responsive to OS [39], we use 4 enzyme antioxidants (GST, CAT, SOD, GPX) as OS injury biomarkers, which have been utilized in previous MR studies [40, 41]. One of the mechanisms through which obesity induces systemic OS is chronic inflammation [34, 35].…”

Investigating the causal impact of polycystic ovary syndrome on gestational diabetes mellitus: a two-sample Mendelian randomization study

“…It’s crucial to highlight that despite the numerous similarities between PCOS and GDM, such as insulin resistance and their association with type 2 diabetes and postpartum impaired glucose metabolism ( 34 ), their relationship has been observed primarily through observational studies, lacking conclusive evidence of a causal link. Presently, there are numerous MR studies on PCOS ( 37 – 41 ). To the best of our knowledge, this is the initial study investigating the causal effects of PCOS and its characteristic indices on GDM.…”

Advancements in the Management of Endocrine System Disorders and Arrhythmias: A Comprehensive Narrative Review

“…PCOS, a common endocrine disorder affecting women, showcases the power of genomic medicine. Recent studies have identified specific genetic variants associated with PCOS, shedding light on its multifactorial aetiology [27]. This genetic insight allows for tailored treatment approaches based on an individual's genetic predisposition, potentially optimizing therapeutic outcomes.…”

“…This genetic insight allows for tailored treatment approaches based on an individual's genetic predisposition, potentially optimizing therapeutic outcomes. The genetic basis of thyroid disorders, including autoimmune conditions like Graves' disease and Hashimoto's thyroiditis, has been elucidated through genomic research [27]. Understanding the genetic susceptibility of patients can guide therapeutic choices, such as the selection of antithyroid drugs or the consideration of thyroidectomy.…”