生活方式因素对衰弱的基因预测效应：来自孟德尔随机化研究的证据。

Genetically-predicted effects of lifestyle factors on frailty: Evidence from Mendelian randomization study.

作者信息

Xin Min, Wang Wenxin, Zhou Ming, Geng Yuhan, Liu Hao, Luo Wenxi, Zhang Gong Zi, Huang Liping

机构信息

Department of Rehabilitation, First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China; School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China.

Department of Rehabilitation, First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China.

出版信息

Arch Gerontol Geriatr. 2025 Feb;129:105662. doi: 10.1016/j.archger.2024.105662. Epub 2024 Oct 17.

DOI:10.1016/j.archger.2024.105662

PMID:39461086

Abstract

OBJECTIVE

To evaluate the causal relationships between genetically predicted lifestyle factors and frailty using Mendelian randomization(MR).

METHODS

We extracted summary data from genome-wide association studies conducted among individuals of European ancestry, examining lifestyle factors such as smoking, alcohol consumption, physical activity, and sedentary behaviors. The outcomes were assessed using Fried Frailty Score (FFS) and Frailty Index (FI). We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent causal effects were primarily estimated using inverse variance weighted methods. Multiple sensitivity and validation analyzes were used.

RESULTS

The IVW analyzes indicated that smoking increased frailty risk (FFS: β = 0.107, 95 % CI = 0.057 to 0.156, P < 0.001; FI: β = 0.899, 95 % CI = 0.016 to 0.191, P = 0.020.), this effect was amplified in the MVMR analysis after adjusting for alcohol consumption. Strenuous sports or other exercise(SSOE) reduced frailty risk (FFS: β = -0.473, 95 % CI = -0.646 to -0.299, P < 0.001; FI: β = -0.423, 95 % CI = -0.692 to -0.154, P = 0.002). Vigorous and moderate-to-vigorous physical activities were significantly related to lower FFS, although no effects were observed on FI. Increased television watching was linked to higher frailty incidence (FFS: β = 0.227, 95 % CI = 0.197 to 0.257, P < 0.001; FI: β = 0.297, 95 % CI = 0.249 to 0.346, P < 0.001), the impact remained persistent in MVMR adjusting for driving and computer use.

CONCLUSION

This study suggests that modifications in smoking, alcohol consumption, and physical activity may help prevent or manage frailty.

摘要

目的

采用孟德尔随机化（MR）评估基因预测的生活方式因素与衰弱之间的因果关系。

方法

我们从对欧洲血统个体进行的全基因组关联研究中提取汇总数据，研究吸烟、饮酒、体育活动和久坐行为等生活方式因素。使用弗里德衰弱评分（FFS）和衰弱指数（FI）评估结果。我们进行了两样本单变量孟德尔随机化（SVMR）和多变量孟德尔随机化（MVMR），以同时评估独立因果效应，主要采用逆方差加权法进行估计。使用了多种敏感性和验证分析。

结果

逆方差加权分析表明，吸烟会增加衰弱风险（FFS：β = 0.107，95%CI = 0.057至0.156，P < 0.001；FI：β = 0.899，95%CI = 0.016至0.191，P = 0.020），在调整饮酒因素后的MVMR分析中，这种效应有所放大。剧烈运动或其他锻炼（SSOE）可降低衰弱风险（FFS：β = -0.473，95%CI = -0.646至-0.299，P < 0.001；FI：β = -0.423，95%CI = -0.692至-0.154，P = 0.002）。剧烈和中等至剧烈的体育活动与较低的FFS显著相关，尽管未观察到对FI有影响。看电视时间增加与更高的衰弱发生率相关（FFS：β = 0.227，95%CI = 0.197至0.257，P < 0.001；FI：β = 0.297，95%CI = 0.249至0.346，P < 0.001），在调整驾驶和使用电脑因素的MVMR分析中，这种影响仍然存在。