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Pàgina inicial > Articles > Articles publicats > Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia |
Data: | 2022 |
Resum: | 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. |
Ajuts: | Instituto de Salud Carlos III PI15/01420 Instituto de Salud Carlos III PI18/01535 Instituto de Salud Carlos III FI19/0352 Instituto de Salud Carlos III FI21/00093 Instituto de Salud Carlos III CP20/00072 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1271 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1577 |
Nota: | Altres ajuts: Ministerio de Ciencia e Innovación; Fondo Europeo de Desarrollo Regional (FEDER); European Social Fund ("Investing in your future"); Generalitat de Catalunya, Departament de Salut (SLT017/20/000233). |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Brain ; Haplotypes ; Humans ; Magnetic Resonance Imaging ; Memory, Short-Term ; Nerve Tissue Proteins ; Polymorphism, Single Nucleotide ; Schizophrenia |
Publicat a: | Scientific reports, Vol. 12 Núm. 1 (december 2022) , p. 7351, ISSN 2045-2322 |
11 p, 1.6 MB |