Evidence of an epistatic effect between Dysbindin-1 and Neuritin-1 genes on the risk for schizophrenia spectrum disorders
| Autor: | Victor Peralta, Jorge Moya-Higueras, C. Prats, M. Parellada, Manuel I. Ibáñez, Bárbara Arias, Edith Pomarol-Clotet, María P. Martín, Ana González-Pinto, Lourdes Fañanás, Mar Fatjó-Vilas |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Neuregulin-1 NRN1 Single-nucleotide polymorphism DTNBP1 Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine medicine Humans Genetic Predisposition to Disease Schizophrenia-spectrum disorders (SSD) Allele Gene Alleles Genetics Neuronal Plasticity Multifactor dimensionality reduction Mechanism (biology) Haplotype Dysbindin Middle Aged medicine.disease Psychiatry and Mental health 030104 developmental biology Schizophrenia Epistatic effect Dystrophin-Associated Proteins Epistasis Female Psychology Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | European psychiatry : the journal of the Association of European Psychiatrists. 40 |
| ISSN: | 1778-3585 0924-9338 |
| Popis: | BackgroundThe interest in studying gene–gene interactions is increasing for psychiatric diseases such as schizophrenia-spectrum disorders (SSD), where multiple genes are involved. Dysbindin-1 (DTNBP1) and Neuritin-1 (NRN1) genes have been previously associated with SSD and both are involved in synaptic plasticity. We aimed to study whether these genes show an epistatic effect on the risk for SSD.MethodsThe sample comprised 388 SSD patients and 397 healthy subjects. Interaction was tested between: (i) three DTNBP1 SNPs (rs2619537, rs2743864, rs1047631) related to changes in gene expression; and (ii) an haplotype in NRN1 previously associated with the risk for SSD (rs645649-rs582262: HAP-risk C-C).ResultsAn interaction between DTNBP1 rs2743864 and NRN1 HAP-risk was detected by using the model based multifactor dimensionality reduction (MB-MDR) approach (P = 0.0049, after permutation procedure), meaning that the risk for SSD is significantly higher in those subjects carrying both the A allele of rs2743864 and the HAP-risk C-C. This interaction was confirmed by using a logistic regression model (P = 0.033, OR (95%CI) = 2.699 (1.08–6.71), R2 = 0.162).DiscussionOur results suggest that DTNBP1 and NRN1 genes show a joint effect on the risk for SSD. Although the precise mechanism underlying this effect is unclear, the fact that these genes have been involved in synaptic maturation, connectivity and glutamate signalling suggests that our findings could be of value as a link to the schizophrenia aetiology. |
| Databáze: | OpenAIRE |
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