Division of Psychiatry, University College London, London, UK; Wellcome Centre for Human Neuroimaging, University College London, London, UK; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
Division of Psychiatry, University College London, London, UK.
Cell Rep. 2021 Mar 16;34(11):108868. doi: 10.1016/j.celrep.2021.108868.
Mismatch negativity (MMN) is a differential electrophysiological response measuring cortical adaptability to unpredictable stimuli. MMN is consistently attenuated in patients with psychosis. However, the genetics of MMN are uncharted, limiting the validation of MMN as a psychosis endophenotype. Here, we perform a transcriptome-wide association study of 728 individuals, which reveals 2 genes (FAM89A and ENGASE) whose expression in cortical tissues is associated with MMN. Enrichment analyses of neurodevelopmental expression signatures show that genes associated with MMN tend to be overexpressed in the frontal cortex during prenatal development but are significantly downregulated in adulthood. Endophenotype ranking value calculations comparing MMN and three other candidate psychosis endophenotypes (lateral ventricular volume and two auditory-verbal learning measures) find MMN to be considerably superior. These results yield promising insights into sensory processing in the cortex and endorse the notion of MMN as a psychosis endophenotype.
失匹配负波（MMN）是一种测量皮质对不可预测刺激适应能力的差异电生理反应。精神分裂症患者的 MMN 一直较弱。然而，MMN 的遗传学尚未被发现，限制了将 MMN 作为精神分裂症的内表型的验证。在这里，我们对 728 个人进行了转录组全基因组关联研究，结果显示 2 个基因（FAM89A 和 ENGASE）的皮质组织表达与 MMN 相关。神经发育表达特征的富集分析表明，与 MMN 相关的基因在产前发育过程中在前额叶皮层过度表达，但在成年后显著下调。比较 MMN 和其他三个候选精神分裂症内表型（侧脑室体积和两个听觉言语学习测量）的内表型等级值计算发现，MMN 明显更优越。这些结果为皮质的感觉处理提供了有希望的见解，并支持将 MMN 作为精神分裂症的内表型的概念。
