Wu Jia-Xin, Deng Fei-Yan, Lei Shu-Feng
Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
Collaborative Innovation Center of Bone and Immunology between Sihong Hospital and Soochow University, Suzhou 215123, China.
Healthcare (Basel). 2023 Jun 29;11(13):1889. doi: 10.3390/healthcare11131889.
Previous associations have been observed not only between risk factors and falls but also between falls and their clinical outcomes based on some cross-sectional designs, but their causal associations were still largely unclear. We performed Mendelian randomization (MR), multivariate Mendelian randomization (MVMR), and mediation analyses to explore the effects of falls. Our study data are mainly based on White European individuals (40-69 years) downloaded from the UK Biobank. MR analyses showed that osteoporosis ( = 0.006), BMI ( = 0.003), sleeplessness ( < 0.001), rheumatoid arthritis ( = 0.001), waist circumference ( < 0.001), and hip circumference ( < 0.001) have causal effects on falls. In addition, for every one standard deviation increase in fall risk, the risk of fracture increased by 1.148 ( < 0.001), the risk of stroke increased by 2.908 ( = 0.003), and a 1.016-fold risk increase in epilepsy ( = 0.009). The MVMR found that sleeplessness is an important risk factor for falls. Finally, our mediation analyses estimated the mediation effects of falls on the hip circumference and fracture ( < 0.001), waist circumference and epilepsy ( < 0.001), and sleeplessness and fracture ( = 0.005). Our study inferred the causal effects between risk factors and falls, falls, and outcomes, and also constructed three causal chains from risk factors → falls → falls outcomes.
以往基于一些横断面设计的研究不仅观察到了风险因素与跌倒之间的关联，还发现了跌倒与其临床结局之间的关联，但其因果关联仍大多不明确。我们进行了孟德尔随机化（MR）、多变量孟德尔随机化（MVMR）和中介分析，以探究跌倒的影响。我们的研究数据主要基于从英国生物银行下载的40至69岁的欧洲白人个体。MR分析表明，骨质疏松症（=0.006）、体重指数（BMI，=0.003）、失眠（<0.001）、类风湿关节炎（=0.001）、腰围（<0.001）和臀围（<0.001）对跌倒有因果效应。此外，跌倒风险每增加一个标准差，骨折风险增加1.148（<0.001），中风风险增加2.908（=0.003），癫痫风险增加1.016倍（=0.009）。MVMR发现失眠是跌倒的一个重要风险因素。最后，我们的中介分析估计了跌倒对臀围与骨折（<0.001）、腰围与癫痫（<0.001）以及失眠与骨折（=0.005）的中介效应。我们的研究推断了风险因素与跌倒、跌倒与结局之间的因果效应，还构建了从风险因素→跌倒→跌倒结局的三条因果链。
