Genetic insights into the risk of frailty on metabolic syndrome and its components: Bidirectional Mendelian randomization study.

IF 3.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Zihang Zhang, Pan Zhang, Feng Zhang, Jinghui Zhong, Wen Sun, Houren Xiong
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引用次数: 0

Abstract

Background and aims: Previous studies have shown that frailty and metabolic syndrome (Mets) share common pathophysiological mechanisms. However, whether the observed association reflects causality requires clarification. We performed a bidirectional Mendelian randomization study to investigate the causal relationship between frailty, Mets, and their individual components.

Methods and results: Summary-level data from GWAS to identify genetic variants associated with frailty, Mets, and its components among individuals of European ancestry. Inverse variance weighting was utilized as the main method. Using bidirectional Mendelian randomization analysis, we found that the risk of frailty was causally associated with an increased risk of MetS (OR: 2.092, 95%CI: 1.564-2.799) and its components, including waist circumference (OR: 1.349, 95 % CI: 1.181-1.541), hypertension (OR: 1.099, 95 % CI: 1.075-1.125), triglycerides (OR: 1.297, 95 % CI: 1.179-1.428). Conversely, the risk of MetS was causally associated with an increased risk of frailty (OR: 1.048; 95 % CI: 1.024-1.073). however, when removing SNPs assocaited with BMI at the loci significance level and performed MVMR, Mets and frailty were not associated.

Conclusion: These findings suggest a bidirectional causal relationship between frailty and MetS, indicating that genetic factors contributing to frailty also increase the risk of MetS and its components, and vice versa. Furthermore, BMI-related SNPs may act as effect modifiers in the association between MetS and frailty. These insights into the shared pathophysiology of frailty and MetS have implications for the prevention and treatment strategies in elderly individuals with MetS.

背景和目的:以往的研究表明,虚弱和代谢综合征(Mets)具有共同的病理生理机制。然而,所观察到的关联是否反映了因果关系还需要澄清。我们进行了一项双向孟德尔随机研究,以调查虚弱、代谢综合征及其各个组成部分之间的因果关系:从全球基因组研究系统(GWAS)中获取摘要级数据,以确定欧洲血统个体中与虚弱、Mets 及其组成部分相关的基因变异。主要方法是采用反方差加权法。通过双向孟德尔随机分析,我们发现虚弱的风险与 MetS 风险的增加存在因果关系(OR:2.092,95%CI:1.564-2.799)。799)及其组成部分,包括腰围(OR:1.349,95 % CI:1.181-1.541)、高血压(OR:1.099,95 % CI:1.075-1.125)、甘油三酯(OR:1.297,95 % CI:1.179-1.428)。相反,MetS 风险与虚弱风险的增加存在因果关系(OR:1.048;95 % CI:1.024-1.073)。然而,当在位点显著性水平上剔除与 BMI 相关的 SNPs 并进行 MVMR 时,Mets 与虚弱并不相关:这些研究结果表明,虚弱与 MetS 之间存在双向因果关系,表明导致虚弱的遗传因素也会增加 MetS 及其组成部分的风险,反之亦然。此外,与体重指数相关的 SNPs 可能是 MetS 与虚弱之间关联的效应调节因子。这些关于虚弱和 MetS 共同病理生理学的见解对患有 MetS 的老年人的预防和治疗策略具有重要意义。
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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
332
审稿时长
57 days
期刊介绍: Nutrition, Metabolism & Cardiovascular Diseases is a forum designed to focus on the powerful interplay between nutritional and metabolic alterations, and cardiovascular disorders. It aims to be a highly qualified tool to help refine strategies against the nutrition-related epidemics of metabolic and cardiovascular diseases. By presenting original clinical and experimental findings, it introduces readers and authors into a rapidly developing area of clinical and preventive medicine, including also vascular biology. Of particular concern are the origins, the mechanisms and the means to prevent and control diabetes, atherosclerosis, hypertension, and other nutrition-related diseases.
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