Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, China.
The Assisted Reproductive Centre, Northwest Women's and Children's Hospital, Xi'an, China.
Front Endocrinol (Lausanne). 2020 Sep 8;11:621. doi: 10.3389/fendo.2020.00621. eCollection 2020.
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that is influenced by both genetic and environmental factors. However, the etiology of PCOS remains unclear. We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of genetically determined metabolites (GDMs) on the risk of PCOS. We used summary level data of a genome-wide association study (GWAS) on 486 metabolites ( = 7,824) as exposure and a PCOS GWAS consisting of 4,138 cases and 20,129 controls as the outcome. Both datasets were obtained from publicly published databases. For each metabolite, a genetic instrumental variable was generated to assess the relationship between the metabolite and PCOS. For MR analysis, we primarily used the standard inverse variance weighted (IVW) method, while three additional methods-the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods-were performed as sensitivity analyses. Using genetic variants as predictors, we observed a robust relationship between epiandrosterone sulfate (EPIA-S) and PCOS ( = 0.0186, = 0.0111; = 0.0154, and = 0.0290). Similarly, 3-dehydrocarnitine, 4-hydroxyhippurate, hexadecanedioate, and β-hydroxyisovalerate may also have causal effects on PCOS development. We identified metabolites that might have causal effects on PCOS development. Our study emphasizes the role of genetic factors underlying the causal relationships between metabolites and PCOS and provides novel insights through the integration of metabolomics and genomics to better understand the mechanisms involved in human disease pathogenesis.
多囊卵巢综合征（PCOS）是一种由遗传和环境因素共同影响的异质性内分泌疾病。然而，PCOS 的病因仍不清楚。我们进行了两样本 Mendelian randomization（MR）分析，以评估遗传决定的代谢物（GDMs）对 PCOS 风险的因果影响。我们使用了一项关于 486 种代谢物（ = 7824）的全基因组关联研究（GWAS）的汇总水平数据作为暴露因素，以及一项由 4138 例病例和 20129 例对照组成的 PCOS GWAS 作为结果。这两个数据集均来自公开发布的数据库。对于每种代谢物，我们生成了一个遗传工具变量来评估代谢物与 PCOS 之间的关系。对于 MR 分析，我们主要使用标准逆方差加权（IVW）方法，同时还进行了三种额外的方法——MR-Egger、加权中位数和 MR-PRESSO（偏倚剩余总和和异常值）方法——作为敏感性分析。使用遗传变异作为预测因子，我们观察到表雄酮硫酸盐（EPIA-S）与 PCOS 之间存在稳健的关系（ = 0.0186， = 0.0111； = 0.0154， = 0.0290）。同样，3-脱氢肉碱、4-羟基马尿酸、十六烷二羧酸和β-羟基异戊酸也可能对 PCOS 的发生有因果影响。我们确定了可能对 PCOS 发生有因果影响的代谢物。我们的研究强调了遗传因素在代谢物与 PCOS 之间因果关系中的作用，并通过代谢组学和基因组学的整合提供了新的见解，以更好地理解人类疾病发病机制中的机制。
