The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated ‘A’ allele (N = 22) or the alternative ‘C’ allele (N = 18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindle amplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function.

中文翻译：

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ZNF804A 的精神分裂症相关变异与健康年轻人的睡眠慢波和纺锤体的经验依赖性动态改变相关

ZNF804A 中的 rs1344706 多态性与精神分裂症密切相关，而精神分裂症又与异常的非快速眼动 (NREM) 睡眠神经生理学相关。为了检查 rs1344706 是否与没有疾病的中间神经生理学特征相关，我们评估了健康参与者的基因型、睡眠神经生理学和睡眠依赖性记忆巩固之间的关系。我们从雅芳父母和儿童纵向研究 (ALSPAC) 出生队列中招募了没有精神疾病史的健康成年男性。参与者在 rs1344706 处是与精神分裂症相关的“A”等位基因（N = 22）或替代“C”等位基因（N = 18）的纯合子。活动图、多导睡眠图 (PSG) 和运动序列任务 (MST) 用于表征日常活动模式，睡眠神经生理学和睡眠依赖的记忆巩固。基因型组的平均 MST 学习和睡眠依赖性表现改善相似，尽管 AA 组的变化更大。在学习后的睡眠期间，CC 参与者表现出增加的慢波 (SW) 和纺锤波振幅，以及 SW 活动在记录电极之间的增强耦合。具有 AA 基因型的 SW 和纺锤体对学习不敏感，而在 MST 训练后 SW 连贯性下降。因此，NREM 神经生理学有力地预测了 CC 携带者的夜间运动记忆巩固程度，而不是 AA 携带者。我们描述了 ZNF804A 中 rs1344706 多态性与协调神经网络活动的变化相关的证据，该活动支持健康人群睡眠期间的离线信息处理。这些发现突出了睡眠神经生理学在绘制精神分裂症相关常见遗传变异对神经回路振荡和功能的影响方面的效用。