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Evidence of an Epistatic Effect Between Dysbindin-1 and Neuritin-1 Genes on the Risk for Schizophrenia Spectrum Disorders

Published online by Cambridge University Press:  14 November 2016

C. Prats ,
B. Arias ,
J. Moya-Higueras ,
E. Pomarol-Clotet ,
M. Parellada ,
A. González-Pinto ,
V. Peralta ,
M.I. Ibáñez ,
M. Martín  and
L. Fañanás
...Show all authors
C. Prats
Affiliation:
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
B. Arias
Affiliation:
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
J. Moya-Higueras
Affiliation:
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Department of Psychology, Faculty of Education, Psychology and Social Work, University of Lleida, Spain
E. Pomarol-Clotet
Affiliation:
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
M. Parellada
Affiliation:
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Servicio de Psiquiatría del Niño y del Adolescente, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IiSGM), Madrid, Spain Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense, Madrid, Spain
A. González-Pinto
Affiliation:
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain BIOARABA Health Research Institute, OSI Araba, University Hospital, Psychiatry Service, University of the Basque Country (EHU/UPV), Vitoria, Spain
V. Peralta
Affiliation:
Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Pamplona, Spain Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
M.I. Ibáñez
Affiliation:
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Department of Basic and Clinical Psychology and Psychobiology, Universitat Jaume I, Castelló, Spain
M. Martín
Affiliation:
Adolescent Unit, CASM Benito Menni, Sant Boi de Llobregat, Spain
L. Fañanás
Affiliation:
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
M. Fatjó-Vilas*
Affiliation:
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
*
* Corresponding author. at: Secció Zoologia i Antropologia Biológica, Facultat de Biologia, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain; FIDMAG Germanes Hospitaláries Research Foundation, Av Jordá 8, 08035 Barcelona, Spain. Tel.: +34 936 529 999x1490. E-mail address:mar.fatjovilas@ub.edu, mfatjo-vilas@fidmag.com (M. Fatjó-Vilas).
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Abstract

Background

The 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.

Methods

The 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).

Results

An 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).

Discussion

Our 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.

Keywords

Schizophrenia-spectrum disorders (SSD)Epistatic effectDTNBP1NRN1
Type
Original article
Information
European Psychiatry , Volume 40 , February 2017 , pp. 60 - 64
Copyright
Copyright © Elsevier Masson SAS 2017

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