探究肌肉疏松症与 11 种呼吸系统疾病的关系:泯灭随机综合分析

IF 3.4 3区 医学 Q2 GERIATRICS & GERONTOLOGY
Yue Su, Youqian Zhang, Di Zhang, Jinfu Xu
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引用次数: 0

摘要

背景肌肉疏松症(Sarcopenia,SP)是一种与衰老有关的肌肉质量和功能丧失,会影响呼吸系统。方法 采用双向单变量孟德尔随机分析法(UVMR)、多变量MR分析法(MVMR)和中介MR分析法,系统研究了SP与11种呼吸系统疾病的遗传因果关系。研究人员将与肌肉疏松症或呼吸系统疾病相关的独立基因组变异确定为工具变量(IVs),并从英国生物库和 FinnGen 获得了全基因组相关研究(GWAS)的汇总数据。 研究人员还进行了 MVMR 分析,以探讨体重指数(BMI)、酒精使用障碍鉴定测试(AUDIT)、吸烟、教育程度(EA)、体力活动和 2 型糖尿病(T2DM)的中介效应。结果基于主要方法的正向 UVMR 分析显示,尘肺病与较高的阑尾瘦肉(ALM)风险相关(OR = 1.01,P = 0.03),而体重指数(10.65%)、吸烟(10.65%)和体育锻炼(17.70%)在尘肺病对 ALM 的影响中起着中介作用。在反向 MR 分析中,我们发现基因预测的 ALM 与肺栓塞(PE)风险的增加显著相关(OR = 1.24,p = 7.21E-05)。慢性阻塞性肺病(COPD)(OR = 0.98,p = 0.002)和肉样瘤病(OR = 1.01,p = 0.004)被认为会增加左手握力(HGS)的损失。相反,左手握力的增加对慢性支气管炎(CB)(OR = 0.35,p = 0.03)、(OR = 0.80,p = 0.02)和哮喘(OR = 0.78,p = 0.04)有保护作用。同样,丧失右侧 HGS 会增加低呼吸道感染(LRTI)(OR = 0.97,p = 0.02)和支气管扩张(OR = 1.01,p = 0.03)的风险,这也是低呼吸道感染和哮喘的独立保护因素。在低 HGS 方面,MVMR 分析后 LRTI 风险增加,反向分析后肉样瘤病和尘肺病风险增加。最后,研究发现哮喘与丧失惯常步行速度有关,反向 MR 分析表明惯常步行速度与 LRTI(OR = 0.32,P = 2.79 × 10-5)、哮喘(OR = 0.24,P = 2.09 × 10-6)、慢性阻塞性肺病(OR = 0.22,P = 6.结论这项数据驱动的磁共振分析显示 SP 与肺部疾病存在双向因果关系,为进一步开展机理和临床研究以了解 SP 与肺部疾病之间的相互影响提供了遗传学证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the relationship between sarcopenia and 11 respiratory diseases: a comprehensive mendelian randomization analysis

Background

Sarcopenia (SP) is an aging-related loss of muscle mass and function, affecting the respiratory system. However, the causality of the association between sarcopenia on lung diseases remains elusive.

Methods

The bidirectional univariate Mendelian randomization (UVMR), multivariate MR (MVMR) analysis, and mediation MR were utilized to systematically investigate the genetic causal relationship of SP and 11 respiratory diseases. Independent genomic variants related to sarcopenia or respiratory diseases were identified as instrumental variables (IVs), and the summary level data of genome-wide associated studies (GWAS) were obtained from the UK biobank and FinnGen. MVMR analysis was conducted to explore the mediation effects of body mass index (BMI), Alcohol Use Disorders Identification Test (AUDIT), smoking, education attainment (EA), physical activity, and Type 2 Diabetes Mellitus (T2DM).

Results

Forward UVMR analysis based on the primary method revealed that pneumoconiosis was associated with a higher risk of appendicular lean mass (ALM) (OR = 1.01, p = 0.03), and BMI (10.65%), smoking (10.65%), and physical activity (17.70%) had a mediating role in the effect of pneumoconiosis on ALM. In reverse MR analysis, we found that genetically predicted ALM was significantly associated with an increased risk of pulmonary embolism (PE) (OR = 1.24, p = 7.21E-05). Chronic obstructive pulmonary disease (COPD) (OR = 0.98, p = 0.002) and sarcoidosis (OR = 1.01, p = 0.004) were identified to increase the loss of left-hand grip strength (HGS). Conversely, the increase in left- HGS presented a protective effect on chronic bronchitis (CB) (OR = 0.35, p = 0.03), (OR = 0.80, p = 0.02), and asthma (OR = 0.78, p = 0.04). Similarly, the loss of the right-HGS elevated the risk of low respiratory tract infection (LRTI) (OR = 0.97, p = 0.02) and bronchiectasis (OR = 1.01, p = 0.03), which is also an independent protective factor for LRTI and asthma. In the aspects of low HGS, the risk of LRTI was increased after MVMR analysis, and the risk of sarcoidosis and pneumoconiosis was elevated in the reverse analysis. Lastly, asthma was found to be related to the loss of the usual walking pace, and the reverse MR analysis suggested a causal relationship between the usual walking pace and LRTI (OR = 0.32, p = 2.79 × 10−5), asthma (OR = 0.24, p = 2.09 × 10−6), COPD (OR = 0.22, p = 6.64 × 10−4), and PE(OR = 0.35, p = 0.03).

Conclusions

This data-driven MR analysis revealed SP was bidirectional causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between SP and lung diseases.

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来源期刊
CiteScore
7.90
自引率
5.00%
发文量
283
审稿时长
1 months
期刊介绍: Aging clinical and experimental research offers a multidisciplinary forum on the progressing field of gerontology and geriatrics. The areas covered by the journal include: biogerontology, neurosciences, epidemiology, clinical gerontology and geriatric assessment, social, economical and behavioral gerontology. “Aging clinical and experimental research” appears bimonthly and publishes review articles, original papers and case reports.
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