Melhuish Beaupre Lindsay M, Tiwari Arun K, Gonçalves Vanessa F, Zai Clement C, Marshe Victoria S, Lewis Cathryn M, Martin Nicholas G, McIntosh Andrew M, Adams Mark J, Baune Bernhard T, Levinson Doug F, Boomsma Dorret I, Penninx Brenda W J H, Breen Gerome, Hamilton Steve, Awasthi Swapnil, Ripke Stephan, Jones Lisa, Jones Ian, Byrne Enda M, Hickie Ian B, Potash James P, Shi Jianxin, Weissman Myrna M, Milaneschi Yuri, Shyn Stanley I, de Geus Eco J C, Willemsen Gonneke, Brown Gregory M, Kennedy James L
Molecular Brain Science Research Department, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Front Psychiatry. 2021 Dec 3;12:734077. doi: 10.3389/fpsyt.2021.734077. eCollection 2021.
The prevalence of insomnia and hypersomnia in depressed individuals is substantially higher than that found in the general population. Unfortunately, these concurrent sleep problems can have profound effects on the disease course. Although the full biology of sleep remains to be elucidated, a recent genome-wide association (GWAS) of insomnia, and other sleep traits in over 1 million individuals was recently published and provides many promising hits for genetics of insomnia in a population-based sample. Using data from the largest available GWAS of insomnia and other sleep traits, we sought to test if sleep variable PRS scores derived from population-based studies predicted sleep variables in samples of depressed cases [Psychiatric Genomics Consortium - Major Depressive Disorder subjects (PGC MDD)]. A leave-one-out analysis was performed to determine the effects that each individual study had on our results. The only significant finding was for insomnia, where -value threshold, = 0.05 was associated with insomnia in our PGC MDD sample ( = 1.75, = 0.006). Our results reveal that <1% of variance is explained by the variants that cover the two significant -value thresholds, which is in line with the fact that depression and insomnia are both polygenic disorders. To the best of our knowledge, this is the first study to investigate genetic overlap between the general population and a depression sample for insomnia, which has important treatment implications, such as leading to novel drug targets in future research efforts.
抑郁症患者中失眠和嗜睡的患病率显著高于普通人群。不幸的是,这些并发的睡眠问题会对病程产生深远影响。尽管睡眠的完整生物学机制仍有待阐明,但最近发表了一项针对超过100万人的失眠及其他睡眠特征的全基因组关联研究(GWAS),该研究在基于人群的样本中为失眠遗传学提供了许多有前景的发现。利用来自现有最大规模的失眠及其他睡眠特征GWAS的数据,我们试图检验基于人群研究得出的睡眠变量PRS评分是否能预测抑郁症患者样本[精神基因组学联盟 - 重度抑郁症受试者(PGC MDD)]中的睡眠变量。进行了留一法分析以确定每项个体研究对我们结果的影响。唯一显著的发现是关于失眠,在我们的PGC MDD样本中,p值阈值p = 0.05与失眠相关(β = 1.75,p = 0.006)。我们的结果表明,覆盖两个显著p值阈值的变异解释的方差不到1%,这与抑郁症和失眠都是多基因疾病这一事实相符。据我们所知,这是第一项研究普通人群和抑郁症样本中失眠的遗传重叠的研究,这具有重要的治疗意义,例如在未来的研究工作中可能会产生新的药物靶点。