背景:观察数据表明情绪不适之间存在联系,比如焦虑和抑郁,和子宫肌瘤(UFs)。然而,需要进一步调查以确定它们之间的因果关系。因此,我们利用双样本孟德尔随机化(MR)评估了4种心理障碍与UF之间的相互因果关系.
方法:评估四种类型的心理困扰(抑郁症状,严重的抑郁症,焦虑或恐慌症发作,情绪波动)和UF,采用双向双样本MR,利用与这些条件相关的单核苷酸多态性(SNP)。单变量MR(UVMR)和多变量MR(MVMR)都主要应用逆方差加权(IVW)作为估计潜在因果效应的方法。诸如MREgger之类的补充方法,加权中位数,简单模式,和加权模式用于验证研究结果。为了评估我们MR结果的稳健性,我们使用Cochran的Q检验和MREgger截距检验进行了敏感性分析。
结果:我们的UVMR分析结果表明,抑郁症状的遗传易感性(比率[OR]=1.563,95%置信区间[CI]=1.209-2.021,P=0.001)和重度抑郁症(MDD)(OR=1.176,95%CI=1.044-1.324,P=0.007)与UF的风险增加有关。此外,IVW模型显示,情绪波动(OR:1.578;95%CI:1.062-2.345;P=0.024)与UFs风险之间存在显著正相关.然而,我们的分析未建立UFs与四种心理困扰之间的因果关系.即使在调整了体重指数(BMI)等混杂因素后,吸烟,酒精消费,以及MVMR中的活产数量,MDD和UFs之间的因果关系仍然显著(OR=1.217,95%CI=1.039-1.425,P=0.015).
结论:我们的研究提供了支持MDD遗传易感性与UFs发病率之间因果关系的证据。这些发现强调了解决心理健康问题的重要性,尤其是抑郁症,在UF的预防和治疗中。
BACKGROUND: Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR).
METHODS: To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran\'s Q-test and the MR Egger intercept test.
RESULTS: The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015).
CONCLUSIONS: Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.