Transcriptome-wide association study reveals two genes that influence mismatch negativity

被引：10

作者：

Bhat, Anjali ^{[1
,3
,9
,11
,12
]}

Irizar, Haritz ^{[1
]}

Thygesen, Johan Hilge ^{[1
]}

Kuchenbaecker, Karoline ^{[1
,5
]}

Pain, Oliver ^{[2
]}

Adams, Rick A. ^{[1
,4
]}

Zartaloudi, Eirini ^{[1
]}

Harju-Seppanen, Jasmine ^{[1
,14
]}

Austin-Zimmerman, Isabelle ^{[1
]}

Wang, Baihan ^{[1
]}

Muir, Rebecca ^{[1
]}

Summerfelt, Ann ^{[6
]}

Du, Xiaoming Michael ^{[6
]}

Bruce, Heather ^{[6
]}

O'Donnell, Patricio ^{[6
,7
,13
]}

Srivastava, Deepak P. ^{[9
,11
,12
]}

Friston, Karl ^{[3
]}

Hong, L. Elliot ^{[6
]}

Hall, Mei-Hua ^{[7
,8
]}

Bramon, Elvira ^{[1
,4
,9
,10
]}

机构：

[1] UCL, Div Psychiat, London, England

[2] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England

[3] UCL, Wellcome Ctr Human Neuroimaging, London, England

[4] UCL, Inst Cognit Neurosci, London, England

[5] UCL, UCL Genet Inst, London, England

[6] Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD USA

[7] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[8] McLean Hosp, Psychosis Neurobiol Lab, 115 Mill St, Belmont, MA 02178 USA

[9] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England

[10] Camden & Islington NHS Fdn Trust, London, England

[11] Kings Coll London, Dept Basic & Clin Neurosci, Inst Psychiat Psychol & Neurosci, London, England

[12] Kings Coll London, MRC, Ctr Neurodev Disorders, London, England

[13] Takeda Pharmaceuticals, Cambridge, MA USA

[14] UCL, Dept Clin Educ & Hlth Psychol, London, England

来源：

CELL REPORTS | 2021年 / 34卷 / 11期

基金：

英国惠康基金; 英国医学研究理事会; 欧盟地平线“2020”; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会;

关键词：

SCHIZOPHRENIA; ENDOPHENOTYPE; HERITABILITY; BRAIN; LOCI; METAANALYSIS; INVOLVEMENT; PSYCHOSIS; CHANNELS; RISK;

D O I：

10.1016/j.celrep.2021.108868

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：13

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