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A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).

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Title: A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).
Authors: Guardiola-Ripoll, Maria (AUTHOR), Almodóvar-Payá, Carmen (AUTHOR), Lubeiro, Alba (AUTHOR), Sotero, Alejandro (AUTHOR), Salvador, Raymond (AUTHOR), Fuentes-Claramonte, Paola (AUTHOR), Salgado-Pineda, Pilar (AUTHOR), Papiol, Sergi (AUTHOR), Ortiz-Gil, Jordi (AUTHOR), Gomar, Jesús J. (AUTHOR), Guerrero-Pedraza, Amalia (AUTHOR), Sarró, Salvador (AUTHOR), Maristany, Teresa (AUTHOR), Molina, Vicente (AUTHOR), Pomarol-Clotet, Edith (AUTHOR), Fatjó-Vilas, Mar (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Oct2022, Vol. 272 Issue 7, p1229-1239. 11p. 1 Color Photograph, 1 Chart, 1 Graph.
Subjects: Schizophrenia, Genes, Short-term memory, Brain imaging, Genotypes, Molecular diagnosis
Abstract: The CACNA1C and the ZNF804A genes are among the most relevant schizophrenia GWAS findings. Recent evidence shows that the interaction of these genes with the schizophrenia diagnosis modulates brain functional response to a verbal fluency task. To better understand how these genes might influence the risk for schizophrenia, we aimed to study the interplay between CACNA1C and ZNF804A on working memory brain functional correlates. The analyses included functional and behavioural N-back task data (obtained from an fMRI protocol) and CACNA1C-rs1006737 and ZNF804A-rs1344706 genotypes for 78 healthy subjects and 78 patients with schizophrenia (matched for age, sex and premorbid IQ). We tested the effects of the epistasis between these genes as well as of the three-way interaction (CACNA1C × ZNAF804A × diagnosis) on working memory-associated activity (N-back: 2-back vs 1-back). We detected a significant CACNA1C × ZNAF804A interaction on working memory functional response in regions comprising the ventral caudate medially and within the left hemisphere, the superior and inferior orbitofrontal gyrus, the superior temporal pole and the ventral-anterior insula. The individuals with the GWAS-identified risk genotypes (CACNA1C-AA/AG and ZNF804A-AA) displayed a reduced working memory modulation response. This genotypic combination was also associated with opposite brain activity patterns between patients and controls. While further research will help to comprehend the neurobiological mechanisms of this interaction, our data highlight the role of the epistasis between CACNA1C and ZNF804A in the functional mechanisms underlying the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).
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  Data: <searchLink fieldCode="AR" term="%22Guardiola-Ripoll%2C+Maria%22">Guardiola-Ripoll, Maria</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Almodóvar-Payá%2C+Carmen%22">Almodóvar-Payá, Carmen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lubeiro%2C+Alba%22">Lubeiro, Alba</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sotero%2C+Alejandro%22">Sotero, Alejandro</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salvador%2C+Raymond%22">Salvador, Raymond</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fuentes-Claramonte%2C+Paola%22">Fuentes-Claramonte, Paola</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salgado-Pineda%2C+Pilar%22">Salgado-Pineda, Pilar</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Papiol%2C+Sergi%22">Papiol, Sergi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ortiz-Gil%2C+Jordi%22">Ortiz-Gil, Jordi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gomar%2C+Jesús+J%2E%22">Gomar, Jesús J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Guerrero-Pedraza%2C+Amalia%22">Guerrero-Pedraza, Amalia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sarró%2C+Salvador%22">Sarró, Salvador</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Maristany%2C+Teresa%22">Maristany, Teresa</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Molina%2C+Vicente%22">Molina, Vicente</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pomarol-Clotet%2C+Edith%22">Pomarol-Clotet, Edith</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fatjó-Vilas%2C+Mar%22">Fatjó-Vilas, Mar</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Oct2022, Vol. 272 Issue 7, p1229-1239. 11p. 1 Color Photograph, 1 Chart, 1 Graph.
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  Data: <searchLink fieldCode="DE" term="%22Schizophrenia%22">Schizophrenia</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Short-term+memory%22">Short-term memory</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+imaging%22">Brain imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Genotypes%22">Genotypes</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+diagnosis%22">Molecular diagnosis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The CACNA1C and the ZNF804A genes are among the most relevant schizophrenia GWAS findings. Recent evidence shows that the interaction of these genes with the schizophrenia diagnosis modulates brain functional response to a verbal fluency task. To better understand how these genes might influence the risk for schizophrenia, we aimed to study the interplay between CACNA1C and ZNF804A on working memory brain functional correlates. The analyses included functional and behavioural N-back task data (obtained from an fMRI protocol) and CACNA1C-rs1006737 and ZNF804A-rs1344706 genotypes for 78 healthy subjects and 78 patients with schizophrenia (matched for age, sex and premorbid IQ). We tested the effects of the epistasis between these genes as well as of the three-way interaction (CACNA1C × ZNAF804A × diagnosis) on working memory-associated activity (N-back: 2-back vs 1-back). We detected a significant CACNA1C × ZNAF804A interaction on working memory functional response in regions comprising the ventral caudate medially and within the left hemisphere, the superior and inferior orbitofrontal gyrus, the superior temporal pole and the ventral-anterior insula. The individuals with the GWAS-identified risk genotypes (CACNA1C-AA/AG and ZNF804A-AA) displayed a reduced working memory modulation response. This genotypic combination was also associated with opposite brain activity patterns between patients and controls. While further research will help to comprehend the neurobiological mechanisms of this interaction, our data highlight the role of the epistasis between CACNA1C and ZNF804A in the functional mechanisms underlying the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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