Transcriptome-wide association study reveals two genes that influence mismatch negativity
| Autor: | Rick A. Adams, Heather Bruce, Karoline Kuchenbaecker, Ann Summerfelt, Oliver Pain, Jasmine Harju-Seppänen, Elvira Bramon, Karl J. Friston, Haritz Irizar, L. Elliot Hong, Deepak Srivastava, Rebecca Muir, Johan H. Thygesen, Anjali Bhat, Xiaoming Michael Du, Patricio O'Donnell, Eirini Zartaloudi, Isabelle Austin-Zimmerman, Baihan Wang, Mei-Hua Hall |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Mismatch negativity Cerebral Ventricles 0302 clinical medicine psychosis Child Aged 80 and over Neurotransmitter Agents MMN prediction error neurodevelopment Intracellular Signaling Peptides and Proteins Middle Aged endophenotype Memory Short-Term Phenotype Schizophrenia mismatch negativity Receptors Virus Female psychological phenomena and processes Adult Psychosis Sensory processing Adolescent Biology behavioral disciplines and activities General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Young Adult Bayesian brain medicine Humans Association (psychology) Aged medicine.disease Cortex (botany) Electrophysiological Phenomena transcriptome-wide association study Intrinsically Disordered Proteins schizophrenia Electrophysiology 030104 developmental biology Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Endophenotype gene expression Transcriptome Neuroscience 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | 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. Graphical abstract Highlights • 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|