@article{28490eb5fbdd4cb481f84080555ff2fe,
title = "Transcriptome-wide association study reveals two genes that influence mismatch negativity",
abstract = "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.",
keywords = "Bayesian brain, endophenotype, gene expression, mismatch negativity, MMN, neurodevelopment, prediction error, psychosis, schizophrenia, transcriptome-wide association study",
author = "Anjali Bhat and Haritz Irizar and Thygesen, {Johan Hilge} and Karoline Kuchenbaecker and Oliver Pain and Adams, {Rick A.} and Eirini Zartaloudi and Jasmine Harju-sepp{\"a}nen and Isabelle Austin-zimmerman and Baihan Wang and Rebecca Muir and Ann Summerfelt and Du, {Xiaoming Michael} and Heather Bruce and Patricio O{\textquoteright}donnell and Srivastava, {Deepak P.} and Karl Friston and Hong, {L. Elliot} and Mei-hua Hall and Elvira Bramon",
note = "Funding Information: We would like to thank all of the participants who took part in this research, as well as the clinical staff who facilitated their involvement. We also thank the UCL Computer Science Cluster team for their excellent IT support. This research was supported by the Medical Research Council ( G0901310 and G1100583 ), the Wellcome Trust (grant nos. 085475/B/08/Z and 085475/Z/08/Z ), and the NIHR Biomedical Research Centre at University College London Hospitals ( UCLH BRC - Mental Health Theme ). A.B. is supported by a Medical Research Council doctoral studentship ( D79/543369/D-OTH/170890 ). H.I. has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement no. 747429 . E.B. thanks the following funders: the National Institute for Health Research ( NIHR200756 ); Mental Health Research UK John Grace QC Scholarship 2018 ; BMA Margaret Temple Fellowships 2016 and 2006; Medical Research Council (MRC) and Korean Health Industry Development Institute Partnering Award ( MC_PC_16014 ); MRC New Investigator Award ( G0901310 ); MRC Centenary Award ( G1100583 ); MRC project grant G1100583 ; a National Institute for Health Research UK post-doctoral fellowship ( PDA/02/06/016 ); the Psychiatry Research Trust ; the Schizophrenia Research Fund ; the Brain and Behaviour Research Foundation {\textquoteright}s NARSAD Young Investigator Awards 2005 and 2008; a Wellcome Trust Research Training Fellowship; Wellcome Trust Case Control Consortium awards ( 085475/B/08/Z and 085475/Z/08/Z ); and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King{\textquoteright}s College London . M.-H.H. thanks the National Institute of Mental Health ( R01MH109687 ) for support. For the Maryland Psychiatric Research Center sample, supports were received from NIH grant nos. R01MH116948 and R01MH112180 and a research contract from Pfizer . We are also grateful for a BMA Margaret Temple grant (2016) to J.H.T., Medical Research Council doctoral studentships to J.H.S. and I.A.-Z., and a China Scholarship Council-UCL Joint Research Scholarship to B.W. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the NIH and by NCI , NHGRI , NHLBI , NIDA , NIMH , and NINDS . Publisher Copyright: {\textcopyright} 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = mar,
day = "16",
doi = "10.1016/j.celrep.2021.108868",
language = "English",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "11",
}