Department of Cardiovascular Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Cardiovascular Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
J Affect Disord. 2024 Feb 15;347:406-413. doi: 10.1016/j.jad.2023.11.052. Epub 2023 Nov 20.
Cardiovascular diseases (CVDs) are significant contributors to global disability and mortality. In addition to traditional cardiovascular risk factors, emerging evidence has suggested that mental health plays a critical role as a risk factor for CVDs. The present study aimed to determine the associations between mood instability and CVDs using Mendelian randomization (MR) analysis.
As instrumental variables, we used 62 independent single-nucleotide polymorphisms associated with mood instability at the genome-wide significance threshold in the UK Biobank. Summary-level data for seven CVDs were obtained from the publicly available genome-wide association studies. The estimates were pooled by using a random-effects inverse-variance weighted method. The results were further validated in sensitivity analysis where different MR methods were compared.
After correcting for multiple testing, our analysis revealed that genetic liability to mood instability was associated with increased odds of six cardiovascular diseases, including deep vein thrombosis (odds ratio (OR) 1.21; confidence interval (CI) 1.03-1.42), pulmonary embolism (OR 1.42; 95 % CI 1.09-1.85), heart failure (OR 1.20; 95 % CI 1.09-1.32), arterial hypertension (OR 1.22; 95 % CI 1.11-1.34), myocardial infarction (OR 1.25; 95 % CI 1.11-1.40), and coronary artery disease (OR 1.25; 95 % CI 1.13-1.39). Further, the genetic liability to mood instability was associated with HDL cholesterol, triglycerides, body mass index, smoking, and depression. In multivariable MR models, the association between genetic liability to mood instability and CVDs remained independent from those cardiovascular risk factors.
The present MR study suggests potential causal associations of genetic liability to mood instability with increased risk of a broad range of CVDs.
心血管疾病（CVDs）是全球残疾和死亡的主要原因。除了传统的心血管危险因素外，新的证据表明，心理健康作为 CVDs 的危险因素起着至关重要的作用。本研究旨在使用孟德尔随机化（MR）分析来确定情绪不稳定与 CVDs 之间的关联。
我们将 62 个与 UK Biobank 中全基因组显著水平相关的情绪不稳定的独立单核苷酸多态性用作工具变量。通过使用随机效应逆方差加权法，汇总了来自公开的全基因组关联研究的七种 CVD 的汇总数据。结果在不同的 MR 方法进行比较的敏感性分析中得到了进一步验证。
在进行多次检验校正后，我们的分析表明，情绪不稳定的遗传易感性与六种心血管疾病的患病风险增加相关，包括深静脉血栓形成（比值比（OR）1.21；95%置信区间（CI）1.03-1.42）、肺栓塞（OR 1.42；95%CI 1.09-1.85）、心力衰竭（OR 1.20；95%CI 1.09-1.32）、动脉高血压（OR 1.22；95%CI 1.11-1.34）、心肌梗死（OR 1.25；95%CI 1.11-1.40）和冠心病（OR 1.25；95%CI 1.13-1.39）。此外，情绪不稳定的遗传易感性与高密度脂蛋白胆固醇、甘油三酯、体重指数、吸烟和抑郁有关。在多变量 MR 模型中，情绪不稳定的遗传易感性与 CVDs 之间的关联仍然独立于这些心血管危险因素。
本 MR 研究表明，情绪不稳定的遗传易感性与广泛的 CVDs 风险增加之间存在潜在的因果关联。
