title: A Highly Polymorphic Copy Number Variant in the NSF Gene is Associated with Cocaine Dependence.
abstract: Cocaine dependence is a complex psychiatric disorder involving both genetic and environmental factors. Several neurotransmitter systems mediate cocaine's effects, dependence and relapse, being the components of the neurotransmitter release machinery good candidates for the disorder. Previously, we identified a risk haplotype for cocaine dependence in the NSF gene, encoding the protein N-Ethylmaleimide-Sensitive Factor essential for synaptic vesicle turnover. Here we examined the possible contribution to cocaine dependence of a large copy number variant (CNV) that encompasses part of the NSF gene. We performed a case-control association study in a discovery sample (359 cases and 356 controls) and identified an association between cocaine dependence and the CNV (P = 0.013), that was confirmed in the replication sample (508 cases and 569 controls, P = 7.1e-03) and in a pooled analysis (P = 1.8e-04), with an over-representation of low number of copies in cases. Subsequently, we studied the functional impact of the CNV on gene expression and found that the levels of two NSF transcripts were significantly increased in peripheral blood mononuclear cells (PBMC) along with the number of copies of the CNV. These results, together with a previous study from our group, support the role of NSF in the susceptibility to cocaine dependence.
authors: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.|Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues, Barcelona, Catalonia, Spain.
authors: Judit
authors: J
authors: Cabana-Domínguez
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Addiction and Dual Diagnosis Unit Clinic Vall Hebron, Psychiatric Services, Hospital Universitari Vall d'Hebron-ASPB, Barcelona, Catalonia, Spain.|Psychiatric Department and Legal Medicine. Universitat Autònoma de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
authors: Carlos
authors: C
authors: Roncero
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Addiction and Dual Diagnosis Unit Clinic Vall Hebron, Psychiatric Services, Hospital Universitari Vall d'Hebron-ASPB, Barcelona, Catalonia, Spain.|Psychiatric Department and Legal Medicine. Universitat Autònoma de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
authors: Lara
authors: L
authors: Grau-López
authors: Addiction and Dual Diagnosis Unit Clinic Vall Hebron, Psychiatric Services, Hospital Universitari Vall d'Hebron-ASPB, Barcelona, Catalonia, Spain.|Psychiatric Department and Legal Medicine. Universitat Autònoma de Barcelona, Catalonia, Spain.
authors: Laia
authors: L
authors: Rodríguez-Cintas
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Addiction and Dual Diagnosis Unit Clinic Vall Hebron, Psychiatric Services, Hospital Universitari Vall d'Hebron-ASPB, Barcelona, Catalonia, Spain.|Psychiatric Department and Legal Medicine. Universitat Autònoma de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
authors: Carmen
authors: C
authors: Barral
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Addiction and Dual Diagnosis Unit Clinic Vall Hebron, Psychiatric Services, Hospital Universitari Vall d'Hebron-ASPB, Barcelona, Catalonia, Spain.
authors: Alfonso C
authors: AC
authors: Abad
authors: Scripps Translational Science Institute, La Jolla, CA, United States of America.
authors: Galina
authors: G
authors: Erikson
authors: Scripps Translational Science Institute, La Jolla, CA, United States of America.
authors: Nathan E
authors: NE
authors: Wineinger
authors: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.|Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues, Barcelona, Catalonia, Spain.
authors: Bàrbara
authors: B
authors: Torrico
authors: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors: Concepció
authors: C
authors: Arenas
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Psychiatric Department and Legal Medicine. Universitat Autònoma de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
authors: Miquel
authors: M
authors: Casas
authors: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.|Psychiatric Genetics Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors: Marta
authors: M
authors: Ribasés
authors: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.|Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues, Barcelona, Catalonia, Spain.
authors: Bru
authors: B
authors: Cormand
authors: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.|Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues, Barcelona, Catalonia, Spain.
authors: Noèlia
authors: N
authors: Fernàndez-Castillo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000235:genetics*
chemical_list: D052066:N-Ethylmaleimide-Sensitive Proteins; C000613831:NSF protein, human