Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study

作者：Yuheng Zhao, Jinglin Pang, Xingyi Fang, Zhaohua Yan, Haili Yang, Qinghua Deng, Tianzhong Ma, Mengqi Lv, Yingying Li, Ziying Tu, Lin Zou · 发表于：Frontiers in Endocrinology · 年份：2024 · DOI：10.3389/fendo.2024.1348368 · 被引用次数：8 · 研究领域：Ovarian function and disorders、Genetic Associations and Epidemiology、Lipid metabolism and disorders

Background Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL,...