Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study

Frontiers in Endocrinology

Endocrinology

Lanlan Chen¹  Shijie Guo²  Yangming Qu²  Ying Liu²  Hui Wu² 

[1]Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, Jilin, China

[2]Department of Neonatology, the First Hospital of Jilin University, Changchun, Jilin, China

关键词: uterine leiomyoma;    risk factor;    Mendelian randomization;    influence;    study;   

DOI  :  10.3389/fendo.2023.1133260

 received in 2023-01-03, accepted in 2023-06-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and objectiveUterine leiomyoma is the most common benign tumor in females of reproductive age. However, its causes have never been fully understood. The objective of our study was to analyze the causal association between various factors and uterine leiomyoma using Mendelian randomization (MR).MethodsGenetic variables associated with risk factors were obtained from genome-wide association studies. Summary-level statistical data for uterine leiomyoma were obtained from FinnGen and the UK Biobank (UKB) consortium. We used inverse variance weighted, MR-Egger, and weighted median methods in univariate analysis. Multivariable MR analysis was used to identify independent risk factors. A fixed-effect model meta-analysis was used to combine the results of the FinnGen and UKB data.ResultsIn the FinnGen data, higher genetically predicted age at natural menopause, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting insulin were associated with an increased risk of uterine leiomyoma, while higher age at menarche was associated with a reduced risk of uterine leiomyoma. Multivariable MR analysis of SBP and DBP showed that higher DBP might be an independent risk factor of uterine leiomyoma. In the UKB data, the results for age at natural menopause, SBP, DBP, and age at menarche were replicated. The result of the meta-analysis suggested that uterine leiomyoma could also be affected by polycystic ovary syndrome (PCOS), endometriosis, and 2-hour glucose level.ConclusionOur MR study confirmed that earlier menstrual age, hypertension, obesity, and elevated 2-hour glucose post-challenge were risk factors for uterine leiomyoma, and the causal relationship between smoking and uterine leiomyoma was ruled out. In addition, later age of menopause and endometriosis were found to increase the risk of uterine leiomyoma, while PCOS was found to decrease the risk.

【 授权许可】

Unknown   
Copyright © 2023 Qu, Chen, Guo, Liu and Wu