NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
Biol Psychiatry. 2021 Nov 1;90(9):621-631. doi: 10.1016/j.biopsych.2021.07.007. Epub 2021 Jul 14.
A range of sleep disturbances are commonly experienced by patients with psychiatric disorders, and genome-wide genetic analyses have shown some significant genetic correlations between these traits. Here, we applied novel statistical genetic methodologies to better characterize the potential shared genetic architecture between sleep-related phenotypes and psychiatric disorders.
Using the MiXeR method, which can estimate polygenic overlap beyond genetic correlation, the shared genetic architecture between major psychiatric disorders (bipolar disorder [N = 51,710], depression [N = 480,359], and schizophrenia [N = 77,096]) and sleep-related phenotypes (chronotype [N = 449,734], insomnia [N = 386,533] and sleep duration [N = 446,118]) were quantified on the basis of genetic summary statistics. Furthermore, the conditional/conjunctional false discovery rate framework was used to identify specific shared loci between these phenotypes, for which positional and functional annotation were conducted with FUMA.
Extensive genetic overlap between the sleep-related phenotypes and bipolar disorder (63%-77%), depression (76%-79%), and schizophrenia (64%-79%) was identified, with moderate levels of congruence between most investigated traits (47%-58%). Specific shared loci were identified for all bivariate analyses, and a subset of 70 credible genes were mapped to these shared loci.
The current results provide evidence for substantial polygenic overlap between psychiatric disorders and sleep-related phenotypes, beyond genetic correlation (|r| = 0.02 to 0.42). Moderate congruency within the shared genetic components suggests a complex genetic relationship and potential subgroups with higher or lower genetic concordance. This work provides new insights and understanding of the shared genetic etiology of sleep-related phenotypes and psychiatric disorders and highlights new opportunities and avenues for future investigation.
精神障碍患者常经历一系列睡眠障碍，全基因组遗传分析表明这些特征之间存在一些显著的遗传相关性。在这里，我们应用新的统计遗传方法来更好地描述睡眠相关表型和精神障碍之间潜在的共同遗传结构。
使用 MiXeR 方法，该方法可以估计遗传相关性之外的多基因重叠，我们基于遗传汇总统计数据来量化主要精神障碍（双相情感障碍 [N=51710]、抑郁症 [N=480359] 和精神分裂症 [N=77096]）和睡眠相关表型（睡眠时型 [N=449734]、失眠 [N=386533] 和睡眠持续时间 [N=446118]）之间的共同遗传结构。此外，使用条件/联合虚假发现率框架来识别这些表型之间的特定共同位点，并使用 FUMA 对其进行位置和功能注释。
确定了睡眠相关表型与双相情感障碍（63%-77%）、抑郁症（76%-79%）和精神分裂症（64%-79%）之间存在广泛的遗传重叠，大多数研究的特征之间存在中等程度的一致性（47%-58%）。所有双变量分析都确定了特定的共同位点，并将 70 个可信基因映射到这些共同位点的子集。
目前的结果提供了精神障碍和睡眠相关表型之间存在大量多基因重叠的证据，超过了遗传相关性（|r|=0.02-0.42）。共同遗传成分内的中等一致性表明存在复杂的遗传关系和潜在的具有更高或更低遗传一致性的亚组。这项工作为睡眠相关表型和精神障碍的共同遗传病因提供了新的见解和理解，并突出了未来研究的新机会和途径。
