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

Oraki Kohshour M; Schulte EC; Heilbronner U; Budde M; Kalman JL; Senner F; Heilbronner M; Reich-Erkelenz D; Schaupp SK; Vogl T; Adorjan K; Anghelescu IG; Arolt V; Baune BT; Dannlowski U; Fallgatter A; Dietrich D; Jäger M; Figge C; Juckel G; Lang FU; Reimer J; Konrad C; Schmauß M; Reininghaus EZ; von Hagen M; Spitzer C; Zimmermann J; Wiltfang J; Nöthen MM; Andlauer TFM; Rietschel M; Witt SH; Degenhardt F; Forstner AJ; Papiol S; Schulze TG; Fischer A; Falkai P

Abstract

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.; Moderate statistical power due to relatively small sample size.; 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.; 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.; 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. - RESULTS - LIMITATIONS - BACKGROUND - METHODS - CONCLUSIONS