Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China.
Endocrine. 2023 Dec;82(3):695-706. doi: 10.1007/s12020-023-03467-8. Epub 2023 Sep 5.
Polycystic ovary syndrome (PCOS) is one of the risk factors for cardiovascular diseases (CVDs). However, the possible association between PCOS and common CVDs remains inconclusive. The aim of this study was to explore the potential relationship between PCOS and CVDs using genetic polymorphisms.
We conducted two-sample Mendelian randomization (MR) analyses. In our study, 14 single nucleotide polymorphisms (SNPs) in Europeans and another 13 SNPs in Asians were applied as instrumental variables for PCOS. The largest published meta-genome-wide association studies of European ancestry and the BioBank Japan Project of Asian ancestry were used to collect the outcome data. MR analysis was performed using inverse variance weighting as the primary method. Several sensitivity analyses and instrumental variable strength evaluations were also performed to verify the reliability of results.
Our analysis revealed that any potential causal association between genetically-predicted PCOS and the risk of CVDs do not exist. These CVDs include peripheral artery disease, atrial fibrillation, arrhythmia, cardiovascular diseases, heart failure, peripheral vascular disease, hypertension, ischemic stroke, myocardial infarction and venous thromboembolisms. Associations could not be found even after the SNPs linked to these possible confounders (body mass index, waist-to-hip ratio, and serum testosterone) were deleted. Sensitivity analysis demonstrated no presence of horizontal pleiotropy or heterogeneity.
The present mendelian randomization study suggests that genetically-predicted PCOS may not be associated with the risk of CVDs.
多囊卵巢综合征(PCOS)是心血管疾病(CVDs)的危险因素之一。然而,PCOS 与常见 CVDs 之间的可能关联仍不确定。本研究旨在利用遗传多态性探讨 PCOS 与 CVDs 之间的潜在关系。
我们进行了两样本 Mendelian 随机化(MR)分析。在我们的研究中,14 个欧洲人群中的单核苷酸多态性(SNPs)和另 13 个亚洲人群中的 SNPs 被用作 PCOS 的工具变量。使用欧洲裔人群中最大的已发表的全基因组关联研究荟萃分析和亚洲裔人群中的日本生物银行项目来收集结局数据。使用逆方差加权作为主要方法进行 MR 分析。还进行了几种敏感性分析和工具变量强度评估,以验证结果的可靠性。
我们的分析表明,遗传预测的 PCOS 与 CVDs 风险之间不存在任何潜在的因果关系。这些 CVDs 包括外周动脉疾病、心房颤动、心律失常、心血管疾病、心力衰竭、外周血管疾病、高血压、缺血性中风、心肌梗死和静脉血栓栓塞。即使在删除与这些可能的混杂因素(体重指数、腰臀比和血清睾酮)相关的 SNPs 后,也没有发现关联。敏感性分析表明不存在水平多效性或异质性。
本 Mendelian 随机化研究表明,遗传预测的 PCOS 与 CVDs 的风险可能无关。