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

Anjali Bhat | Zendy; Haritz Irizar | Zendy; Johan H. Thygesen | Zendy; Karoline Kuchenbaecker | Zendy; Oliver Pain | Zendy; Rick A. Adams | Zendy; Eirini Zartaloudi | Zendy; Jasmine HarjuSeppänen | Zendy; Isabelle Austin-Zimmerman | Zendy; Baihan Wang | Zendy; Rebecca Muir | Zendy; Ann Summerfelt | Zendy; Xiaoming Du | Zendy; Heather Bruce | Zendy; Patricio O’Donnell | Zendy; Deepak P. Srivastava | Zendy; Karl Friston | Zendy; L. Elliot Hong | Zendy; MeiHua Hall | Zendy; Elvira Bramon | Zendy

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

Author(s) -

Anjali Bhat,

Haritz Irizar,

Johan H. Thygesen,

Karoline Kuchenbaecker,

Oliver Pain,

Rick A. Adams,

Eirini Zartaloudi,

Jasmine HarjuSeppänen,

Isabelle Austin-Zimmerman,

Baihan Wang,

Rebecca Muir,

Ann Summerfelt,

Xiaoming Du,

Heather Bruce,

Patricio O’Donnell,

Deepak P. Srivastava,

Karl Friston,

L. Elliot Hong,

MeiHua Hall,

Elvira Bramon

Publication year - 2021

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2021.108868

Subject(s) - mismatch negativity , endophenotype , psychosis , psychology , sensory processing , auditory cortex , transcriptome , neuroscience , electroencephalography , audiology , biology , sensory system , medicine , gene expression , gene , genetics , cognition , psychiatry

Summary 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.

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