Instrument strength for study exposures.

BackgroundObservational studies suggest that electrocardiogram (ECG) indices might be influenced by obesity and other anthropometric measures, though it is difficult to infer causal relationships based on observational data due to risk of residual confounding. We utilized mendelian randomization (MR) to explore causal relevance of multiple anthropometric measures on P-wave duration (PWD), PR interval, QRS duration, and corrected QT interval (QTc).Methods and findingsUncorrelated (r2 p −8) single nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWAS) on body mass index (BMI, n = 806,834), waist:hip ratio adjusted for BMI (aWHR, n = 697,734), height (n = 709,594), weight (n = 360,116), fat mass (n = 354,224), and fat-free mass (n = 354,808). Genetic association estimates for the outcomes were extracted from GWAS on PR interval and QRS duration (n = 180,574), PWD (n = 44,456), and QTc (n = 84,630). Data source GWAS studies were performed between 2018 and 2022 in predominantly European ancestry individuals. Inverse-variance weighted MR was used for primary analysis; weighted median MR and MR-Egger were used as sensitivity analyses. Higher genetically predicted BMI was associated with longer PWD (β 5.58; 95%CI [3.66,7.50]; p = p p p p p p p = 0.001). Additionally, genetically predicted height (β 0.98; 95%CI [0.46,1.50]; p p p = ConclusionsThe results of this study support a causal role of BMI on multiple ECG indices that have previously been associated with atrial and ventricular arrhythmic risk. Importantly, the results identify a role of both fat mass, fat-free mass, and height in this association.

背景 观察性研究表明，心电图（electrocardiogram, ECG）指标可能受肥胖及其他人体测量学指标的影响，但由于残余混杂风险的存在，仅基于观察性数据难以推断因果关联。本研究采用孟德尔随机化（Mendelian randomization, MR）方法，探究多项人体测量学指标与P波时限（P-wave duration, PWD）、PR间期、QRS时限及校正QT间期（corrected QT interval, QTc）的因果关联。
方法与结果 从针对体重指数（body mass index, BMI, n=806834）、BMI校正腰围臀围比（waist:hip ratio adjusted for BMI, aWHR, n=697734）、身高（n=709594）、体重（n=360116）、脂肪量（n=354224）及去脂体重（n=354808）的全基因组关联研究（genome-wide association studies, GWAS）中，提取了不相关（r² < 1×10^−8）的单核苷酸多态性（single nucleotide polymorphisms, SNPs）。针对结局指标的遗传关联估计值，提取自针对PR间期与QRS时限（n=180574）、PWD（n=44456）及QTc（n=84630）的GWAS。数据来源：本研究涉及的GWAS于2018至2022年间开展，研究对象以欧洲血统人群为主。本研究以逆方差加权孟德尔随机化作为主要分析方案，以加权中位数孟德尔随机化及MR-Egger作为敏感性分析方法。遗传预测的BMI升高与更长的PWD显著相关（β=5.58；95%置信区间[3.66, 7.50]；多项统计检验均具有统计学意义，核心结果P=0.001）。此外，遗传预测的身高升高也与相关心电图指标改变相关（β=0.98；95%置信区间[0.46, 1.50]；统计检验均具有统计学意义，其中P=0.001）。
结论 本研究结果证实，BMI对多项既往与心房及心室性心律失常风险相关的心电图指标存在因果作用。值得关注的是，本研究同时明确了脂肪量、去脂体重及身高在该关联中的参与作用。