Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia
Abstract The DISC1 gene is one of the most relevant susceptibility genes for psychosis. However, the complex genetic landscape of this locus, which includes protective and risk variants in interaction, may have hindered consistent conclusions on how DISC1 contributes to schizophrenia (SZ) liability....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10660-8 |
| _version_ | 1811305883112570880 |
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| author | Maria Guardiola-Ripoll Alejandro Sotero-Moreno Carmen Almodóvar-Payá Noemí Hostalet Amalia Guerrero-Pedraza Núria Ramiro Jordi Ortiz-Gil Bárbara Arias Mercè Madre Joan Soler-Vidal Raymond Salvador Peter J. McKenna Edith Pomarol-Clotet Mar Fatjó-Vilas |
| author_facet | Maria Guardiola-Ripoll Alejandro Sotero-Moreno Carmen Almodóvar-Payá Noemí Hostalet Amalia Guerrero-Pedraza Núria Ramiro Jordi Ortiz-Gil Bárbara Arias Mercè Madre Joan Soler-Vidal Raymond Salvador Peter J. McKenna Edith Pomarol-Clotet Mar Fatjó-Vilas |
| author_sort | Maria Guardiola-Ripoll |
| collection | DOAJ |
| description | Abstract The DISC1 gene is one of the most relevant susceptibility genes for psychosis. However, the complex genetic landscape of this locus, which includes protective and risk variants in interaction, may have hindered consistent conclusions on how DISC1 contributes to schizophrenia (SZ) liability. Analysis from haplotype approaches and brain-based phenotypes can contribute to understanding DISC1 role in the neurobiology of this disorder. We assessed the brain correlates of DISC1 haplotypes associated with SZ through a functional neuroimaging genetics approach. First, we tested the association of two DISC1 haplotypes, the HEP1 (rs6675281-1000731-rs999710) and the HEP3 (rs151229-rs3738401), with the risk for SZ in a sample of 138 healthy subjects (HS) and 238 patients. This approach allowed the identification of three haplotypes associated with SZ (HEP1-CTG, HEP3-GA and HEP3-AA). Second, we explored whether these haplotypes exerted differential effects on n-back associated brain activity in a subsample of 70 HS compared to 70 patients (diagnosis × haplotype interaction effect). These analyses evidenced that HEP3-GA and HEP3-AA modulated working memory functional response conditional to the health/disease status in the cuneus, precuneus, middle cingulate cortex and the ventrolateral and dorsolateral prefrontal cortices. Our results are the first to show a diagnosis-based effect of DISC1 haplotypes on working memory-related brain activity, emphasising its role in SZ. |
| first_indexed | 2024-04-13T08:33:17Z |
| format | Article |
| id | doaj.art-516f15b0aae94c4cafb989237b8f06ef |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T08:33:17Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-516f15b0aae94c4cafb989237b8f06ef2022-12-22T02:54:10ZengNature PortfolioScientific Reports2045-23222022-05-0112111110.1038/s41598-022-10660-8Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophreniaMaria Guardiola-Ripoll0Alejandro Sotero-Moreno1Carmen Almodóvar-Payá2Noemí Hostalet3Amalia Guerrero-Pedraza4Núria Ramiro5Jordi Ortiz-Gil6Bárbara Arias7Mercè Madre8Joan Soler-Vidal9Raymond Salvador10Peter J. McKenna11Edith Pomarol-Clotet12Mar Fatjó-Vilas13FIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationHospital San RafaelFIDMAG Germanes Hospitalàries Research FoundationCIBERSAM (Biomedical Research Network in Mental Health), Instituto de Salud Carlos IIIAddictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant PauFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationAbstract The DISC1 gene is one of the most relevant susceptibility genes for psychosis. However, the complex genetic landscape of this locus, which includes protective and risk variants in interaction, may have hindered consistent conclusions on how DISC1 contributes to schizophrenia (SZ) liability. Analysis from haplotype approaches and brain-based phenotypes can contribute to understanding DISC1 role in the neurobiology of this disorder. We assessed the brain correlates of DISC1 haplotypes associated with SZ through a functional neuroimaging genetics approach. First, we tested the association of two DISC1 haplotypes, the HEP1 (rs6675281-1000731-rs999710) and the HEP3 (rs151229-rs3738401), with the risk for SZ in a sample of 138 healthy subjects (HS) and 238 patients. This approach allowed the identification of three haplotypes associated with SZ (HEP1-CTG, HEP3-GA and HEP3-AA). Second, we explored whether these haplotypes exerted differential effects on n-back associated brain activity in a subsample of 70 HS compared to 70 patients (diagnosis × haplotype interaction effect). These analyses evidenced that HEP3-GA and HEP3-AA modulated working memory functional response conditional to the health/disease status in the cuneus, precuneus, middle cingulate cortex and the ventrolateral and dorsolateral prefrontal cortices. Our results are the first to show a diagnosis-based effect of DISC1 haplotypes on working memory-related brain activity, emphasising its role in SZ.https://doi.org/10.1038/s41598-022-10660-8 |
| spellingShingle | Maria Guardiola-Ripoll Alejandro Sotero-Moreno Carmen Almodóvar-Payá Noemí Hostalet Amalia Guerrero-Pedraza Núria Ramiro Jordi Ortiz-Gil Bárbara Arias Mercè Madre Joan Soler-Vidal Raymond Salvador Peter J. McKenna Edith Pomarol-Clotet Mar Fatjó-Vilas Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia Scientific Reports |
| title | Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
| title_full | Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
| title_fullStr | Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
| title_full_unstemmed | Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
| title_short | Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
| title_sort | combining fmri and disc1 gene haplotypes to understand working memory related brain activity in schizophrenia |
| url | https://doi.org/10.1038/s41598-022-10660-8 |
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