Transcriptome-wide association study reveals two genes that influence mismatch negativity.
Transcriptome-wide association study reveals two genes that influence mismatch negativity.
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DOI：
10.1016/j.celrep.2021.108868
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发表时间：
2021-03-16
期刊：
影响因子：
8.8
通讯作者：
Bramon E
中科院分区：
文献类型：
--
作者：
Bhat A;Irizar H;Thygesen JH;Kuchenbaecker K;Pain O;Adams RA;Zartaloudi E;Harju-Seppänen J;Austin-Zimmerman I;Wang B;Muir R;Summerfelt A;Du XM;Bruce H;O'Donnell P;Srivastava DP;Friston K;Hong LE;Hall MH;Bramon E
失配负性（MMN）是一种差异电生理反应，测量皮层对不可预测刺激的适应性。MMN在精神病患者中持续减弱。然而，MMN的遗传学是未知的，限制了MMN作为精神病内表型的有效性。在这里，我们对728个个体进行了转录组相关性研究，揭示了两个基因（FAM89A和ENGASE）在皮质组织中的表达与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期间倾向于在额叶皮层过度表达，但在成年期显著下调。内表型排序值计算比较MMN和其他三种候选精神病内表型（侧脑室容积和两种听-言语学习测量）发现MMN相当优越。这些结果对皮层的感觉处理产生了有希望的见解，并支持MMN作为精神病内表型的概念。FAM89A和ENGASE的表达与失配负性（MMN）降低相关调节神经递质水平的基因在MMN转录组关联中增加影响MMN的基因在成人大脑皮层中表达不足MMN在精神病的内表型中排在言语记忆和心室容积之前。Bhat等人鉴定出FAM89A和ENGASE两个基因在皮质组织中的表达与失配负性（MMN）负相关。脑皮层对意外感觉刺激反应的电生理测量。他们在这些关联中发现了神经传递调节基因的富集，并证实MMN是精神病的一种内表型。
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. Expression of FAM89A and ENGASE is associated with reduced mismatch negativity (MMN) Genes regulating neurotransmitter levels increase in MMN transcriptome-wide association Genes influencing MMN are underexpressed in adult brain cortex MMN ranks above verbal memory and ventricular volume as psychosis endophenotype Bhat et al. identify two genes, FAM89A and ENGASE, whose expression in cortical tissue is negatively associated with mismatch negativity (MMN), an electrophysiological measure of cortical responses to unexpected sensory stimuli. They find enrichment of neurotransmission-regulating genes in these associations and endorse MMN as an endophenotype for psychosis.
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影响因子：
10.6
作者：
Erickson MA;Ruffle A;Gold JM
通讯作者：
Gold JM
影响因子：
5.7
作者：
Doeller, CF;Opitz, B;Schröger, E
通讯作者：
Schröger, E
DOI：
10.1098/rstb.2005.1622
发表时间：
2005-04-29
影响因子：
6.3
作者：
Friston, KJ
通讯作者：
Friston, KJ
DOI：
10.1016/j.clinph.2008.11.029
发表时间：
2009-03
期刊：
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
影响因子：
--
作者：
Garrido MI;Kilner JM;Stephan KE;Friston KJ
通讯作者：
Friston KJ
影响因子：
11
作者：
Bergen, S. E.;O'Dushlaine, C. T.;Ripke, S.;Lee, P. H.;Ruderfer, D. M.;Akterin, S.;Moran, J. L.;Chambert, K. D.;Handsaker, R. E.;Backlund, L.;Osby, U.;McCarroll, S.;Landen, M.;Scolnick, E. M.;Magnusson, P. K. E.;Lichtenstein, P.;Hultman, C. M.;Purcell, S. M.;Sklar, P.;Sullivan, P. F.
通讯作者：
Sullivan, P. F.