Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study.
Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study.
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睡眠、重度抑郁症和阿尔茨海默病：一项孟德尔随机化研究。
DOI：
10.1212/wnl.0000000000010463
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发表时间：
2020-10-06
期刊：
影响因子：
9.9
通讯作者：
Dehghan A
中科院分区：
文献类型：
--
作者：
Huang J;Zuber V;Matthews PM;Elliott P;Tzoulaki J;Dehghan A
探讨睡眠、重度抑郁障碍(MDD)和阿尔茨海默病(AD)之间的因果关系。我们进行了双向2样本孟德尔随机化分析。遗传关联是从英国生物库(n=446,118)、精神病学基因组学联盟(n=18,759)和国际阿尔茨海默氏症基因组学项目(n=63,926)中现有的最大的全基因组关联研究中获得的。我们使用逆方差加权孟德尔随机化方法估计因果效应，并使用加权中位数和孟德尔随机化-Egger进行敏感性分析来检验多效性效应。我们发现，较高的AD风险与“早起的人”(优势比[OR]1.01，p=0.001)、睡眠时间较短(自我报告：β=−0.006，p=1.9×10−4；基于加速度计：β=−0.015，p=6.9x10−5)，报告长睡眠的可能性较小(β=−0.003，p=7.3x10−7)，最不活跃的5小时的较早计时(β=−0.024，p=1.7x10−13)，以及经过多次比较调整后的较少睡眠次数(β=−0.025，p=5.7x10−14)。我们还发现，AD风险越高，失眠风险越低(OR0.99，p=7×10−13)。然而，我们没有发现证据表明这些异常的睡眠模式与AD有因果关系，也没有证据表明MDD与AD风险之间存在显著的因果关系。我们发现，阿尔茨海默病可能会因果地影响睡眠模式。然而，我们没有找到证据支持睡眠模式紊乱对AD的因果作用，也没有证据表明MDD和AD之间存在因果关系。
To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD). We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance–weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization–Egger for sensitivity analyses to test for pleiotropic effects. We found that higher risk of AD was significantly associated with being a “morning person” (odds ratio [OR] 1.01, p = 0.001), shorter sleep duration (self-reported: β = −0.006, p = 1.9 × 10−4; accelerometer based: β = −0.015, p = 6.9 × 10−5), less likely to report long sleep (β = −0.003, p = 7.3 × 10−7), earlier timing of the least active 5 hours (β = −0.024, p = 1.7 × 10−13), and a smaller number of sleep episodes (β = −0.025, p = 5.7 × 10−14) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, p = 7 × 10−13). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.