UNASSIGNED: 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.
UNASSIGNED: 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, P = 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.
UNASSIGNED: 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.
■我们收集了UL的遗传关联数据(35,474例),高血压(129,909例),HDP(妊娠期高血压8,502例,子痫前期6663例,子痫452例),收缩压(SBP)和舒张压(DBP)(均为757,601名参与者)来自已发表的全基因组关联研究(GWAS)。与UL表型相关的单核苷酸多态性(SNPs)被用作工具变量,和高血压,HDP的三种子类型,SBP和DBP作为结果。采用逆方差加权(IVW)方法作为因果推断的主要方法。异质性使用Cochran的Q检验进行评估,使用MR-Egger回归和MR多效性残差和异常值(MR-PRESSO)测试进行敏感性分析,以评估工具变量的多效性。使用PhenoScanner搜索来删除混杂的SNP。使用加权中位数和加权模式等方法评估结果的鲁棒性和可靠性。
■IVW分析显示遗传预测的UL和SBP之间呈正相关[比值比(OR)=1.67,95%置信区间(CI):1.24〜2.25,P=0.0007],UL和高血压之间没有发现统计关联,HDP,或DBP。MR-Egger回归表明,上述因果关系不受水平多效性的影响。加权中值方法和加权模型产生了与IVW相似的结果。
■基于大规模人口GWAS数据,我们的MR分析提示UL和SBP之间存在因果关系.因此,女性与UL,尤其是孕妇,要注意监测自己的血压水平。对于已经患有UL的高血压患者,UL干预措施可作为控制血压的潜在治疗方法.