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. Copyright 2021 The Author(s)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. Copyright 2021 The Author(s)