Zhu Qi, Chen Qiyu, Tian Ying, Zhang Jing, Ran Rui, Shu Shiyu
Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 404100, China.
J Cardiovasc Dev Dis. 2023 Feb 10;10(2):76. doi: 10.3390/jcdd10020076.
Observational studies have found an association between increased whole body water mass (BWM) and atrial fibrillation (AF). However, the causality has yet to be confirmed. To provide feasible protective measures on disease development, we performed Mendelian randomization (MR) design to estimate the potential causal relationship between increased BWM and AF.
We implemented a two-sample MR study to assess whether increased BWM causally influences AF incidence. For exposure, 61 well-powered genetic instruments extracted from UK Biobank ( = 331,315) were used as the proxies of BWM. Summary genetic data of AF were obtained from FinnGen (Ncase = 22,068; Ncontrol = 116,926). Inverse-variance weighted (IVW), MR-Egger and weighted median methods were selected to infer causality, complemented with a series of sensitivity analyses. MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and Radial MR were employed to identify outliers. Furthermore, risk factor analyses were performed to investigate the potential mechanisms between increased BWM and AF.
Genetic predisposition to increased BWM was demonstrated to be significantly associated with AF in the IVW model (OR = 2.23; 95% CI = 1.47-3.09; = 1.60 × 10), and the result was consistent in other MR approaches. There was no heterogeneity or pleiotropy detected in sensitivity analysis. MR-PRESSO identified no outliers with potential pleiotropy after excluding outliers by Radial MR. Furthermore, our risk factor analyses supported a positive causal effect of genetic predicted increased BWM on edematous diseases.
MR estimates showed that a higher BWM could increase the risk of AF. Pathological edema is an important intermediate link mediating this causal relationship.
观察性研究发现全身水含量（BWM）增加与心房颤动（AF）之间存在关联。然而，因果关系尚未得到证实。为了提供关于疾病发展的可行保护措施，我们进行了孟德尔随机化（MR）设计，以估计BWM增加与AF之间的潜在因果关系。
我们实施了一项两样本MR研究，以评估BWM增加是否因果性地影响AF发病率。对于暴露因素，从英国生物银行（n = 331,315）提取的61个效力强大的基因工具被用作BWM的替代指标。AF的汇总基因数据来自芬兰基因库（病例数 = 22,068；对照数 = 116,926）。选择逆方差加权（IVW）、MR-Egger和加权中位数方法来推断因果关系，并辅以一系列敏感性分析。采用MR-多效性残差和异常值（MR-PRESSO）以及径向MR来识别异常值。此外，进行了风险因素分析，以研究BWM增加与AF之间的潜在机制。
在IVW模型中，BWM增加的遗传易感性被证明与AF显著相关（OR = 2.23；95%CI = 1.47 - 3.09；P = 1.60×10），并且该结果在其他MR方法中一致。敏感性分析未检测到异质性或多效性。通过径向MR排除异常值后，MR-PRESSO未识别出具有潜在多效性的异常值。此外，我们的风险因素分析支持遗传预测的BWM增加对水肿性疾病有正向因果效应。
MR估计表明，较高的BWM可能增加AF的风险。病理性水肿是介导这种因果关系的重要中间环节。
