Elucidating the Linkage Between Obesity-Related Body Fat Indicators and Atrial Fibrillation: Supported by Evidence From Mendelian Randomization and Mediation Analyses

IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Junxian Wang, Shengzhi Zhou, Xiaoming Xie, Wenlin Liu
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引用次数: 0

Abstract

Objectives

To elucidating the linkage between obesity-associated body fat indicators and atrial fibrillation (AF) using Mendelian Randomization (MR) and mediation analysis.

Methods

The study utilized three independent genome-wide association study (GWAS) datasets, with containing over 450 000 individuals each, to represent body fat indicators as the exposure variable. Additionally, two summary genetic datasets of AF were utilized as the clinical outcome. Single nucleotide polymorphisms (SNPs) with p-values less than 5 × 10−10 were identified as instrumental variables (IVs) for MR analysis. The primary analysis method employed was the inverse-variance weighting (IVW) model, supplemented by three additional models: MR-Egger regression, weighted median, and maximum likelihood. Sensitivity analysis was conducted, encompassing tests for heterogeneity and horizontal pleiotropy, utilizing Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to validate the reliability of the findings. Furthermore, a mediation analysis was conducted to explore potential mediators involved in the pathogenesis of AF.

Results

The IVW model demonstrated that per 1-SD increase in body fat indicators (body fat percentage, whole body fat mass, and trunk fat mass) is associated with an elevated risk of AF, with values of 63.1%, 55.0%, and 55.8% respectively. All three supplementary models arrived comparable conclusions with IVW model. The sensitivity analysis confirmed the absence of horizontal pleiotropy, thereby validating the reliability of the findings. Additionally, the mediation study indicates that hypertension and sleep apnea syndrome are identified as significant mediators during the pathogenesis of AF.

Conclusions

The study reveals that individuals with a higher body fat percentage tend to exhibit a heightened genetic predisposition for susceptibility to AF. Meanwhile, hypertension and sleep apnea syndrome have been identified as key mediators contributing to the pathogenesis of AF.

Abstract Image

阐明肥胖相关体脂指标与房颤之间的联系:来自孟德尔随机化和中介分析的证据支持
目的通过孟德尔随机化(MR)和中介分析,探讨肥胖相关体脂指标与房颤(AF)的关系。方法利用三个独立的全基因组关联研究(GWAS)数据集,每个数据集包含超过45万个体,将体脂指标作为暴露变量。此外,两组房颤基因汇总数据集作为临床结果。p值小于5 × 10−10的单核苷酸多态性(snp)被确定为MR分析的工具变量(IVs)。采用的主要分析方法是反方差加权(IVW)模型,辅以MR-Egger回归、加权中位数和最大似然三种模型。进行敏感性分析,包括异质性和水平多效性测试,利用Cochran’s Q、MR-Egger截距和MR-PRESSO测试来验证结果的可靠性。结果IVW模型显示,体脂指标(体脂百分比、全身脂肪质量和躯干脂肪质量)每增加1 sd,与房颤风险升高相关,分别为63.1%、55.0%和55.8%。所有三个补充模型都得到了与IVW模型相当的结论。敏感性分析证实没有水平多效性,从而验证了研究结果的可靠性。此外,中介研究表明,高血压和睡眠呼吸暂停综合征是房颤发病过程中的重要中介。结论研究表明,体脂率较高的个体易患房颤的遗传易感性较高。高血压和睡眠呼吸暂停综合征已被确定为房颤发病的关键介质。
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来源期刊
Clinical Cardiology
Clinical Cardiology 医学-心血管系统
CiteScore
5.10
自引率
3.70%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Clinical Cardiology provides a fully Gold Open Access forum for the publication of original clinical research, as well as brief reviews of diagnostic and therapeutic issues in cardiovascular medicine and cardiovascular surgery. The journal includes Clinical Investigations, Reviews, free standing editorials and commentaries, and bonus online-only content. The journal also publishes supplements, Expert Panel Discussions, sponsored clinical Reviews, Trial Designs, and Quality and Outcomes.
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