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Association between mitochondria-related genes and cognitive performance in the PsyCourse Study
Mojtaba Oraki Kohshour1, Eva C Schulte2, Urs Heilbronner3
1Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Journal of Affective Disorders
|January 9, 2023
Summary
Mitochondria-related gene COA8 is associated with short-term memory performance in individuals with severe psychiatric disorders. This finding may improve understanding of cognitive deficits in mental illness.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Mitochondria are crucial for cellular energy production via oxidative phosphorylation (OXPHOS).
- Variations in mitochondria-related genes can impact OXPHOS protein function and potentially increase mental illness risk.
- Investigating the genetic underpinnings of cognitive function is vital for understanding mental disorders.
Purpose of the Study:
- To examine the association between mitochondria-related genes and cognitive performance.
- To assess the role of genetic risk burden in mitochondria-related genes concerning cognitive abilities.
- To explore potential links between mitochondrial dysfunction and cognitive deficits in psychiatric populations.
Main Methods:
- Utilized cross-sectional data from 1320 individuals with severe psychiatric disorders and 466 neurotypical controls (PsyCourse Study).
- Analyzed cognitive performance using Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test.
- Conducted association analyses between cognitive tests, single-nucleotide polymorphisms (SNPs) in mitochondria-related genes, and schizophrenia polygenic risk score (PRS) using PLINK 1.9 and R.
Main Results:
- Identified a significant association between the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus and the Verbal Digit Span (forward) test (FDR-adjusted p < 0.05).
- The COA8 gene is part of the OXPHOS pathway and its association suggests a link to short-term memory.
- No significant association was found between mitochondrial polygenic risk score (PRS) and any cognitive tests analyzed.
Conclusions:
- The study identified a novel association between the COA8 gene and short-term memory, a key cognitive domain.
- COA8 encodes a poorly characterized mitochondrial protein, and its role in apoptosis warrants further investigation.
- These findings, though requiring replication due to moderate statistical power, may enhance understanding of cognitive impairment in mental disorders.
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