一项调查多囊卵巢综合征与睾酮之间因果关系的双向两样本孟德尔随机化研究
A two-sample bidirectional Mendelian randomization study investigating the causal relationship between polycystic ovary syndrome and testosterone
濮义福1
作者信息
- 1. 四川大学华西第二医院遗传代谢性疾病及围生医学实验室/出生缺陷与相关妇儿疾病教育部重点实验室,四川成都 610041
- 折叠
摘要
目的 多囊卵巢综合征(PCOS)通常存在睾酮水平升高,表现为临床和(或)生化高雄.然而,PCOS与睾酮(T)之间的因果关系仍然不明确.尚不清楚PCOS是否导致T水平增加,或者升高的T水平是否有助于PCOS疾病的发生.因此本研究旨在探究PCOS与T水平之间的因果关系.方法 基于公开可获取的全基因组关联分析数据,进行了双向两样本孟德尔随机化(MR)研究.研究了 PCOS、总睾酮(TT)和生物活性睾酮水平.主要的分析方法是逆方差加权(IVW)法.使用MR-Egger截距评估了工具变量的多效性.使用Q值和P值评估了异质性.结果 遗传测定的PCOS不会导致TT或生物活性睾酮的增加(所有P＞0.05).然而,总睾酮会增加PCOS疾病的发生(IVW,OR:1.256,95％CI:1.056～1.495,P=0.010).此外,生物活性睾酮也会增加 PCOS 疾病的发生(IVW,OR:1.495,95％CI:1.275～1.752,P=7.440 × 10-7).F统计量表明不存在弱工具变量.使用留一法进行了敏感性分析.未观察到工具变量存在多效性,结果稳健,结论可靠.结论 这项研究证明了 T(无论是TT还是生物活性睾酮)与PCOS之间存在因果关系.发现更高水平的T与患PCOS的风险增加相关,结果强有力地支持了 T诱导的PCOS理论,特别强调了在研究中利用T诱导的PCOS模型的有效性.
Abstract
Objective Polycystic ovary syndrome(PCOS)commonly presents with elevated testosterone levels,manifesting as clinical and/or biochemical hyperandrogenism.Yet,the causal link between PCOS and testosterone(T)remains ambiguous.It's uncertain whether PCOS leads to increased T levels or if elevated T levels contribute to the development of PCOS.This study aims to investigate the causal relationship between PCOS and T levels.Methods Two-sample bidirectional Mendelian randomization(MR)studies were performed based on publicly available statistics from genome-wide association studies.PCOS,total T(TT)and bioavailable T levels were studied.The main analytical method used was inverse variance weighting(IVW).Pleiotropy was evaluated using the MR-Egger intercept.Q and P values were used to assess heterogeneity.Results Genetic determination of PCOS does not lead to an increase in total testosterone(TT)or bioactive testosterone(all P＞0.05).However,elevated TT is associated with an increased risk of PCOS(IVW,OR:1.256,95％CI:1.056-1.495,P=0.010).Additionally,bioactive T also increases the occurrence of PCOS(IVW,OR:1.495,95％CI:1.275-1.752,P=7.440×10-7).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.Conclusion This study demonstrates a causal relationship between T(both TT and bioavailable T)and PCOS,indicating that higher levels of T are associated with an increased risk of developing PCOS.These findings strongly support the theory of androgen-induced PCOS,particularly emphasizing the validity of utilizing the androgen-induced PCOS model in research.
关键词
多囊卵巢综合征/睾酮/高雄激素血症/孟德尔随机化/因果Key words
polycystic ovary syndrome/testosterone/hyperandrogenism/Mendelian randomization study/causal relationship引用本文复制引用
出版年
2024
NETL
NSTL
万方数据