Association between mitochondria-related genes and cognitive performance in the PsyCourse Study
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...
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| creator | Oraki Kohshour, Mojtaba Schulte, Eva C. Heilbronner, Urs Budde, Monika Kalman, Janos L. Senner, Fanny Heilbronner, Maria Reich-Erkelenz, Daniela Schaupp, Sabrina K. Vogl, Thomas Adorjan, Kristina Anghelescu, Ion-George Arolt, Volker Baune, Bernhardt T. Dannlowski, Udo Dietrich, Detlef Fallgatter, Andreas Figge, Christian Jäger, Markus Lang, Fabian U. Juckel, Georg Konrad, Carsten Reimer, Jens Reininghaus, Eva Z. Schmauß, Max Spitzer, Carsten von Hagen, Martin Wiltfang, Jens Zimmermann, Jörg Andlauer, Till F.M. Nöthen, Markus M. Degenhardt, Franziska Forstner, Andreas J. Rietschel, Marcella Witt, Stephanie H. Fischer, Andre Falkai, Peter Papiol, Sergi Schulze, Thomas G. |
| description | 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.
We found a significant association (FDR-adjusted p |
| doi_str_mv | 10.1016/j.jad.2023.01.013 |
| format | Article |
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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.
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.
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.
•Mitochondria generate energy through oxidative phosphorylation (OXPHOS) pathway.•Variation in mitochondria-related genes can affect key proteins involved in OXPHOS.•The protein COA8 is associated with cognitive performance.•Mitochondrial genetic risk burden has no clear effects on cognitive function.</description><identifier>ISSN: 0165-0327</identifier><identifier>EISSN: 1573-2517</identifier><identifier>DOI: 10.1016/j.jad.2023.01.013</identifier><identifier>PMID: 36621676</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Brain disorders ; COA8 ; Cognition ; Cognitive Dysfunction - complications ; Cognitive Dysfunction - genetics ; Cross-Sectional Studies ; Humans ; Mitochondria ; Mitochondria - genetics ; Neuropsychological Tests ; Oxidative phosphorylation ; Schizophrenia - complications ; Short-term memory</subject><ispartof>Journal of affective disorders, 2023-03, Vol.325, p.1-6</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-5d3146c6247b4d300b694dacd0c4679533220b521fba38462feffb1d896c03563</citedby><cites>FETCH-LOGICAL-c353t-5d3146c6247b4d300b694dacd0c4679533220b521fba38462feffb1d896c03563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165032723000204$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36621676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oraki Kohshour, Mojtaba</creatorcontrib><creatorcontrib>Schulte, Eva C.</creatorcontrib><creatorcontrib>Heilbronner, Urs</creatorcontrib><creatorcontrib>Budde, Monika</creatorcontrib><creatorcontrib>Kalman, Janos L.</creatorcontrib><creatorcontrib>Senner, Fanny</creatorcontrib><creatorcontrib>Heilbronner, Maria</creatorcontrib><creatorcontrib>Reich-Erkelenz, Daniela</creatorcontrib><creatorcontrib>Schaupp, Sabrina K.</creatorcontrib><creatorcontrib>Vogl, Thomas</creatorcontrib><creatorcontrib>Adorjan, Kristina</creatorcontrib><creatorcontrib>Anghelescu, Ion-George</creatorcontrib><creatorcontrib>Arolt, Volker</creatorcontrib><creatorcontrib>Baune, Bernhardt T.</creatorcontrib><creatorcontrib>Dannlowski, Udo</creatorcontrib><creatorcontrib>Dietrich, Detlef</creatorcontrib><creatorcontrib>Fallgatter, Andreas</creatorcontrib><creatorcontrib>Figge, Christian</creatorcontrib><creatorcontrib>Jäger, Markus</creatorcontrib><creatorcontrib>Lang, Fabian U.</creatorcontrib><creatorcontrib>Juckel, Georg</creatorcontrib><creatorcontrib>Konrad, Carsten</creatorcontrib><creatorcontrib>Reimer, Jens</creatorcontrib><creatorcontrib>Reininghaus, Eva Z.</creatorcontrib><creatorcontrib>Schmauß, Max</creatorcontrib><creatorcontrib>Spitzer, Carsten</creatorcontrib><creatorcontrib>von Hagen, Martin</creatorcontrib><creatorcontrib>Wiltfang, Jens</creatorcontrib><creatorcontrib>Zimmermann, Jörg</creatorcontrib><creatorcontrib>Andlauer, Till F.M.</creatorcontrib><creatorcontrib>Nöthen, Markus M.</creatorcontrib><creatorcontrib>Degenhardt, Franziska</creatorcontrib><creatorcontrib>Forstner, Andreas J.</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Witt, Stephanie H.</creatorcontrib><creatorcontrib>Fischer, Andre</creatorcontrib><creatorcontrib>Falkai, Peter</creatorcontrib><creatorcontrib>Papiol, Sergi</creatorcontrib><creatorcontrib>Schulze, Thomas G.</creatorcontrib><title>Association between mitochondria-related genes and cognitive performance in the PsyCourse Study</title><title>Journal of affective disorders</title><addtitle>J Affect Disord</addtitle><description>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.
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.
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.
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Academic</collection><jtitle>Journal of affective disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oraki Kohshour, Mojtaba</au><au>Schulte, Eva C.</au><au>Heilbronner, Urs</au><au>Budde, Monika</au><au>Kalman, Janos L.</au><au>Senner, Fanny</au><au>Heilbronner, Maria</au><au>Reich-Erkelenz, Daniela</au><au>Schaupp, Sabrina K.</au><au>Vogl, Thomas</au><au>Adorjan, Kristina</au><au>Anghelescu, Ion-George</au><au>Arolt, Volker</au><au>Baune, Bernhardt T.</au><au>Dannlowski, Udo</au><au>Dietrich, Detlef</au><au>Fallgatter, Andreas</au><au>Figge, Christian</au><au>Jäger, Markus</au><au>Lang, Fabian U.</au><au>Juckel, Georg</au><au>Konrad, Carsten</au><au>Reimer, Jens</au><au>Reininghaus, Eva Z.</au><au>Schmauß, Max</au><au>Spitzer, Carsten</au><au>von Hagen, Martin</au><au>Wiltfang, Jens</au><au>Zimmermann, Jörg</au><au>Andlauer, Till F.M.</au><au>Nöthen, Markus M.</au><au>Degenhardt, Franziska</au><au>Forstner, Andreas J.</au><au>Rietschel, Marcella</au><au>Witt, Stephanie H.</au><au>Fischer, Andre</au><au>Falkai, Peter</au><au>Papiol, Sergi</au><au>Schulze, Thomas G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between mitochondria-related genes and cognitive performance in the PsyCourse Study</atitle><jtitle>Journal of affective disorders</jtitle><addtitle>J Affect Disord</addtitle><date>2023-03-15</date><risdate>2023</risdate><volume>325</volume><spage>1</spage><epage>6</epage><pages>1-6</pages><issn>0165-0327</issn><eissn>1573-2517</eissn><abstract>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.
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.
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.
•Mitochondria generate energy through oxidative phosphorylation (OXPHOS) pathway.•Variation in mitochondria-related genes can affect key proteins involved in OXPHOS.•The protein COA8 is associated with cognitive performance.•Mitochondrial genetic risk burden has no clear effects on cognitive function.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>36621676</pmid><doi>10.1016/j.jad.2023.01.013</doi><tpages>6</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Brain disorders COA8 Cognition Cognitive Dysfunction - complications Cognitive Dysfunction - genetics Cross-Sectional Studies Humans Mitochondria Mitochondria - genetics Neuropsychological Tests Oxidative phosphorylation Schizophrenia - complications Short-term memory |
| title | Association between mitochondria-related genes and cognitive performance in the PsyCourse Study |
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