Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Aging (Albany NY). 2023 Dec 12;15(23):14066-14085. doi: 10.18632/aging.205290.
Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is uncertain. We conducted a two-sample Mendelian randomization study to investigate the associations. Genetic instruments associated with the exposures at the genome-wide significance level ( < 5 × 10) were selected from corresponding genome-wide association studies ( = 143,677 to 703,901 individuals). Summary-level data for the frailty index were obtained from the UK Biobank ( = 164,610) and Swedish TwinGene ( = 10,616). The β of the frailty index was 0.15 ( = 3.88 × 10) for 1 standard deviation increase in the prevalence of smoking initiation, 0.19 ( = 3.54 × 10) for leisure screen time, 0.13 ( = 5.26 × 10) for body mass index and 0.13 ( = 1.80 × 10) for waist circumference. There was a suggestive association between genetically predicted higher birth weight and moderate-to-vigorous intensity physical activity with the decreased risk of the frailty index. We observed no causal association between genetically predicted age of smoking initiation and alcoholic drinks per week with the frailty index. This study supports the causal roles of smoking initiation, leisure screen time, overall obesity, and abdominal obesity in frailty. The possible association between higher birth weight, proper physical activity and a decreased risk of frailty needs further confirmation.
肥胖、出生体重和生活方式因素已被观察性研究发现与虚弱的风险相关，但这些关联是否具有因果关系尚不确定。我们进行了一项两样本孟德尔随机化研究来探讨这些关联。从相应的全基因组关联研究中选择与暴露相关的全基因组显著水平（<5×10）的遗传工具（= 143677 至 703901 人）。从英国生物银行（= 164610）和瑞典 TwinGene（= 10616）获得虚弱指数的汇总水平数据。对于吸烟起始的流行率增加 1 个标准差，虚弱指数的 β 为 0.15（= 3.88×10），休闲屏幕时间为 0.19（= 3.54×10），体重指数为 0.13（= 5.26×10），腰围为 0.13（= 1.80×10）。较高的出生体重和中等至剧烈强度的体力活动与虚弱指数降低之间存在暗示性关联。我们没有观察到遗传预测的吸烟起始年龄和每周酒精饮料摄入量与虚弱指数之间的因果关联。这项研究支持吸烟起始、休闲屏幕时间、整体肥胖和腹部肥胖与虚弱之间的因果作用。较高的出生体重、适当的体力活动与虚弱风险降低之间的可能关联需要进一步证实。
