Yang Fangkun, Chen Songzan, Qu Zihao, Wang Kai, Xie Xiaojie, Cui Hanbin
Department of Cardiology, Ningbo Hospital of Zhejiang University (Ningbo First Hospital), Ningbo, China.
Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Aging Neurosci. 2021 Nov 8;13:757388. doi: 10.3389/fnagi.2021.757388. eCollection 2021.
To investigate the causal association of domain-specific sedentary behaviors with cerebrovascular diseases and neurodegenerative diseases, and the potential mediators among these associations. Genetic instruments were identified for television watching, computer use and driving behavior from a genome-wide association study including 408,815 subjects. Mendelian randomization (MR) analysis was used to estimate the causal effect of sedentary behaviors on the cerebrovascular diseases and neurodegenerative diseases. Multivariable MR analysis was applied to adjust potential confounding factors, and mediation analysis was conducted to explore potential mediators. Genetically predisposition to 1.5 h/day increase in leisure time watching television was associated with increased risk of all-cause stroke [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15-1.52, -value for MR-Egger method ( ) = 0.11, = 37%, Cochrane's Q = 212, -value for Cochran Q test ( ) < 0.001], and ischemic stroke (OR = 1.28, 95%CI = 1.10-1.49, = 0.04, = 35%, Cochrane's Q = 206, = 0.002). Interestingly, television watching may decrease the risk of Parkinson's disease (OR = 0.65, 95%CI = 0.50-0.84, = 0.47, = 19%, Cochrane's Q = 157, = 0.04). Television watching was a detrimental factor of cognitive performance (estimate = -0.46, 95%CI = -0.55 - -0.37, = 0.001, = 85%, Cochrane's Q = 862, < 0.001). Sensitivity analyses using leave out method and MR-PRESSO method suggested weak evidence of pleiotropy. We provided genetic evidence for the causal association of television watching with increased risk of all-cause stroke and ischemic stroke, decreased risk of Parkinson's disease, and worse cognitive performance. The results should be interpreted with caution considering the pleiotropy.
为了研究特定领域久坐行为与脑血管疾病和神经退行性疾病之间的因果关系，以及这些关联中的潜在中介因素。从一项包含408,815名受试者的全基因组关联研究中确定了用于看电视、使用电脑和驾驶行为的遗传工具。采用孟德尔随机化（MR）分析来估计久坐行为对脑血管疾病和神经退行性疾病的因果效应。应用多变量MR分析来调整潜在的混杂因素，并进行中介分析以探索潜在的中介因素。每天休闲时间看电视增加1.5小时的遗传易感性与全因中风风险增加相关[比值比（OR）=1.32，95%置信区间（CI）=1.15 - 1.52，MR-Egger方法的P值（P）=0.11，I² = 37%，Cochrane's Q = 212，Cochran Q检验的P值（P）<0.001]，以及缺血性中风（OR = 1.28，95%CI = 1.10 - 1.49，P = 0.04，I² = 35%，Cochrane's Q = 206，P = 0.002）。有趣的是，看电视可能会降低帕金森病的风险（OR = 0.65，95%CI = 0.50 - 0.84，P = 0.47，I² = 19%，Cochrane's Q = 157，P = 0.04）。看电视是认知能力的一个不利因素（估计值=-0.46，95%CI = -0.55 - -0.37，P = 0.001，I² = 85%，Cochrane's Q = 862，P < 0.001）。使用留一法和MR-PRESSO方法的敏感性分析表明存在弱的多效性证据。我们提供了遗传证据，证明看电视与全因中风和缺血性中风风险增加、帕金森病风险降低以及认知能力下降之间存在因果关系。考虑到多效性，对结果的解释应谨慎。
