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Association between mitochondria-related genes and cognitive performance in the PsyCourse Study.

Journal of affective disorders

Authors: Mojtaba Oraki Kohshour, Eva C Schulte, Urs Heilbronner, Monika Budde, Janos L Kalman, Fanny Senner, Maria Heilbronner, Daniela Reich-Erkelenz, Sabrina K Schaupp, Thomas Vogl, Kristina Adorjan, Ion-George Anghelescu, Volker Arolt, Bernhardt T Baune, Udo Dannlowski, Detlef Dietrich, Andreas Fallgatter, Christian Figge, Markus Jäger, Fabian U Lang, Georg Juckel, Carsten Konrad, Jens Reimer, Eva Z Reininghaus, Max Schmauß, Carsten Spitzer, Martin von Hagen, Jens Wiltfang, Jörg Zimmermann, Till F M Andlauer, Markus M Nöthen, Franziska Degenhardt, Andreas J Forstner, Marcella Rietschel, Stephanie H Witt, Andre Fischer, Peter Falkai, Sergi Papiol, Thomas G Schulze

BACKGROUND: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance.

METHODS: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program.

RESULTS: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests.

LIMITATIONS: Moderate statistical power due to relatively small sample size.

CONCLUSIONS: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

Copyright © 2023 Elsevier B.V. All rights reserved.

PMID: 36621676

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