title: Involvement of NRN1 gene in schizophrenia-spectrum and bipolar disorders and its impact on age at onset and cognitive functioning.
abstract: OBJECTIVE
  Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF.
  
  
  METHODS
  The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF.
  
  
  RESULTS
  The frequency of the haplotype C-C (rs645649-rs582262) was significantly increased in patients compared to controls (P = 0.0043), while the haplotype T-C-C-T-C-A (rs3763180-rs10484320-rs4960155-rs9379002-rs9405890-rs1475157) was more frequent in controls (P = 3.1 × 10(-5)). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P = 0.005).
  
  
  CONCLUSIONS
  Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF.
authors.affiliation: a Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona , Barcelona , Spain ; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain;|b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;
authors.forename: Mar
authors.initials: M
authors.lastname: Fatjó-Vilas
authors.affiliation: a Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona , Barcelona , Spain ; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain;|b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;
authors.forename: Claudia
authors.initials: C
authors.lastname: Prats
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|c FIDMAG Germanes Hospitalàries, Research Foundation , Barcelona , Spain ;
authors.forename: Edith
authors.initials: E
authors.lastname: Pomarol-Clotet
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|d Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona , Barcelona , Spain ;|e Institut d'investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Departament de Psiquiatria i Psicobiologia Clínica, Facultat de Medicina, Universitat de Barcelona , Barcelona , Spain ;
authors.forename: Luisa
authors.initials: L
authors.lastname: Lázaro
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|f Servicio de Psiquiatría del Niño y del Adolescente , Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IiSGM); Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense , Madrid , Spain ;
authors.forename: Carmen
authors.initials: C
authors.lastname: Moreno
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|g Psychiatry Service, University Hospital of Alava-Santiago, EMBREC, EHU/UPV University of the Basque Country, Kronikgune , Vitoria , Spain ;
authors.forename: Itxaso
authors.initials: I
authors.lastname: González-Ortega
authors.affiliation: d Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona , Barcelona , Spain ;
authors.forename: Sara
authors.initials: S
authors.lastname: Lera-Miguel
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|h Centre de Salut Mental d'Adults de Lleida, Servei de Psiquiatria, Salut Mental i Addiccions, Hospital Universitari Santa Maria de Lleida , Lleida , Spain ;
authors.forename: Salvador
authors.initials: S
authors.lastname: Miret
authors.affiliation: i Àrea d'Adolescents, Complex Assistencial en Salut Mental Benito Menni, Sant Boi De Llobregat , Spain ;
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Muñoz
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|j Departament de Psicologia Bàsica , Clínica i Psicobiologia, Facultat de Ciències de la Salut, Universitat Jaume I , Castelló , Spain ;
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ibáñez
authors.affiliation: h Centre de Salut Mental d'Adults de Lleida, Servei de Psiquiatria, Salut Mental i Addiccions, Hospital Universitari Santa Maria de Lleida , Lleida , Spain ;
authors.forename: Sílvia
authors.initials: S
authors.lastname: Campanera
authors.affiliation: i Àrea d'Adolescents, Complex Assistencial en Salut Mental Benito Menni, Sant Boi De Llobregat , Spain ;
authors.forename: Maria
authors.initials: M
authors.lastname: Giralt-López
authors.affiliation: k Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Pamplona Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA) , Pamplona , Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Cuesta
authors.affiliation: k Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Pamplona Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA) , Pamplona , Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Peralta
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|j Departament de Psicologia Bàsica , Clínica i Psicobiologia, Facultat de Ciències de la Salut, Universitat Jaume I , Castelló , Spain ;
authors.forename: Generós
authors.initials: G
authors.lastname: Ortet
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|f Servicio de Psiquiatría del Niño y del Adolescente , Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IiSGM); Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense , Madrid , Spain ;
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|g Psychiatry Service, University Hospital of Alava-Santiago, EMBREC, EHU/UPV University of the Basque Country, Kronikgune , Vitoria , Spain ;
authors.forename: Ana
authors.initials: A
authors.lastname: González-Pinto
authors.affiliation: b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;|c FIDMAG Germanes Hospitalàries, Research Foundation , Barcelona , Spain ;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McKenna
authors.affiliation: a Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona , Barcelona , Spain ; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain;|b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003071:Cognition; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007361:Intelligence Tests; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D013030:Spain; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; C484539:NRN1 protein, human; D009479:Neuropeptides; C579455:BDNF protein, human
keywords: BDNF; NRN1; Schizophrenia-spectrum and bipolar disorders; age at onset; intelligence