Obstetrics and Gynecology Department, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Endocrinol (Lausanne). 2024 May 10;15:1373724. doi: 10.3389/fendo.2024.1373724. eCollection 2024.
Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure.
We collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran's Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode.
The IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW.
Based on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.
高血压和妊娠高血压疾病（HDP）是不同阶段女性常见的疾病，影响着女性身心健康，后者对后代的影响不容忽视。观察性研究已经探讨了子宫肌瘤（UL）与上述情况之间的相关性，但这种关系仍不清楚。在这项研究中，我们采用两样本孟德尔随机化（MR）分析来评估 UL 与高血压、HDP 以及血压之间的关联。
我们从已发表的全基因组关联研究（GWAS）中收集了 UL（35474 例）、高血压（129909 例）、HDP（妊娠期高血压 8502 例、子痫前期 6663 例、子痫 452 例）、收缩压（SBP）和舒张压（DBP）（757601 例参与者）的遗传关联数据。与 UL 表型相关的单核苷酸多态性（SNP）被用作工具变量，高血压、HDP 的三种亚型、SBP 和 DBP 被用作结局。采用逆方差加权（IVW）法作为因果推断的主要方法。采用 Cochran's Q 检验评估异质性，采用 MR-Egger 回归和 MR 偏倚残差和异常值（MR-PRESSO）检验评估工具变量的偏倚。使用 PhenoScanner 搜索去除混杂 SNP。采用加权中位数和加权模式等方法评估结果的稳健性和可靠性。
IVW 分析显示，遗传预测的 UL 与 SBP 呈正相关[比值比（OR）=1.67，95%置信区间（CI）：1.24~2.25， = 0.0007]，而 UL 与高血压、HDP 或 DBP 之间无统计学关联。MR-Egger 回归表明，上述因果关系不受水平偏倚的影响。加权中位数法和加权模型得出的结果与 IVW 相似。
基于大规模人群 GWAS 数据，我们的 MR 分析提示 UL 与 SBP 之间存在因果关系。因此，患有 UL 的女性，尤其是孕妇，应注意监测血压水平。对于已经患有 UL 的高血压患者，针对 UL 的干预措施可能成为管理血压的潜在治疗方法。
