Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Department of Psychiatry, University of Colorado School of Medicine, Denver, Colorado, USA.
Addict Biol. 2022 Jul;27(4):e13184. doi: 10.1111/adb.13184.
Sleep problems and substance use frequently co-occur. While substance use can result in specific sleep deficits, genetic pleiotropy could explain part of the relationship between sleep and substance use and use disorders. Here we use the largest publicly available genome-wide summary statistics of substance use behaviours (N = 79,729-632,802) and sleep/activity phenotypes to date (N = 85,502-449,734) to (1) assess the genetic overlap between substance use behaviours and both sleep and circadian-related activity measures, (2) estimate clusters from genetic correlations and (3) test processes of causality versus genetic pleiotropy. We found 31 genetic correlations between substance use and sleep/activity after Bonferroni correction. These patterns of overlap were represented by two genetic clusters: (1) tobacco use severity (age of first regular tobacco use and smoking cessation) and sleep health (sleep duration, sleep efficiency and chronotype) and (2) substance consumption/problematic use (drinks per day and cigarettes per day, cannabis use disorder, opioid use disorder and problematic alcohol use) and sleep problems (insomnia, self-reported short sleep duration, increased number of sleep episodes, increased sleep duration variability and diurnal inactivity) and measures of circadian-related activity (L5, M10 and sleep midpoint). Latent causal variable analyses determined that horizontal pleiotropy (rather than genetic causality) underlies a majority of the associations between substance use and sleep/circadian related measures, except one plausible genetically causal relationship for opioid use disorder on self-reported long sleep duration. Results show that shared genetics are likely a mechanism that is at least partly responsible for the overlap between sleep and substance use traits.
睡眠问题和物质使用经常同时发生。虽然物质使用会导致特定的睡眠不足，但遗传多效性可以解释部分睡眠与物质使用和使用障碍之间的关系。在这里，我们使用迄今为止最大的公开可用的物质使用行为全基因组汇总统计数据（N=79729-632802）和睡眠/活动表型（N=85502-449734）来（1）评估物质使用行为与睡眠和昼夜节律相关活动测量之间的遗传重叠，（2）估计遗传相关性聚类，（3）测试因果关系与遗传多效性的过程。在经过 Bonferroni 校正后，我们发现物质使用与睡眠/活动之间有 31 个遗传相关性。这些重叠模式由两个遗传聚类表示：（1）烟草使用严重程度（首次定期使用烟草和戒烟年龄）和睡眠健康（睡眠持续时间、睡眠效率和昼夜节律类型）和（2）物质消费/问题使用（每天饮酒量和吸烟量、大麻使用障碍、阿片类药物使用障碍和问题性酒精使用）和睡眠问题（失眠、自我报告的睡眠时间短、睡眠发作次数增加、睡眠持续时间变异性增加和日间不活动）和昼夜节律相关活动测量（L5、M10 和睡眠中点）。潜在因果变量分析确定，水平多效性（而不是遗传因果关系）是物质使用与睡眠/昼夜节律相关测量之间大多数关联的基础，只有一种与自我报告的长睡眠时间有关的阿片类药物使用障碍的遗传因果关系是合理的。结果表明，共同的遗传可能是导致睡眠和物质使用特征重叠的至少部分原因的机制。
