Background

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.

Methods

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.

Results

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.

Conclusions

The current results provide evidence for substantial polygenic overlap between psychiatric disorders and sleep-related phenotypes, beyond genetic correlation (|r_g| = 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.

中文翻译：

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表征精神疾病和睡眠相关表型之间的遗传重叠

背景

精神疾病患者通常会经历一系列睡眠障碍，全基因组遗传分析显示这些特征之间存在一些显着的遗传相关性。在这里，我们应用了新的统计遗传方法来更好地描述睡眠相关表型和精神疾病之间潜在的共享遗传结构。

方法

使用 MiXeR 方法，可以估计遗传相关性之外的多基因重叠，主要精神疾病（双相障碍 [ N  = 51,710]、抑郁症 [ N  = 480,359] 和精神分裂症 [ N  = 77,096]）和睡眠相关之间的共享遗传结构表型（睡眠类型 [ N  = 449,734]、失眠 [ N  = 386,533] 和睡眠持续时间 [ N  = 446,118]）基于遗传汇总统计进行量化。此外，使用条件/连接错误发现率框架来识别这些表型之间的特定共享位点，使用 FUMA 对其进行位置和功能注释。

结果

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，大多数研究的性状之间具有中等水平的一致性(47%–58%)。所有双变量分析都确定了特定的共享基因座，并将 70 个可信基因的子集映射到这些共享基因座。

结论

目前的结果为精神疾病和睡眠相关表型之间存在大量多基因重叠提供了证据，超出了遗传相关性（| r _g | = 0.02 至 0.42）。共享遗传成分中的中等一致性表明复杂的遗传关系和具有较高或较低遗传一致性的潜在亚群。这项工作为睡眠相关表型和精神疾病的共同遗传病因提供了新的见解和理解，并突出了未来调查的新机会和途径。