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Several neurotransmitter systems mediate cocaine\u2019s 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 <jats:italic>NSF<\/jats:italic> 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 <jats:italic>NSF<\/jats:italic> 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 (<jats:italic>P<\/jats:italic>\u2009=\u20090.013), that was confirmed in the replication sample (508 cases and 569 controls, <jats:italic>P<\/jats:italic>\u2009=\u20097.1e-03) and in a pooled analysis (<jats:italic>P<\/jats:italic>\u2009=\u20091.8e-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 <jats:italic>NSF<\/jats:italic> 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 <jats:italic>NSF<\/jats:italic> in the susceptibility to cocaine dependence.<\/jats:p>","DOI":"10.1038\/srep31033","type":"journal-article","created":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T09:24:11Z","timestamp":1470648251000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Highly Polymorphic Copy Number Variant in the NSF Gene is Associated with Cocaine Dependence"],"prefix":"10.1038","volume":"6","author":[{"given":"Judit","family":"Cabana-Dom\u00ednguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Roncero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Grau-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Rodr\u00edguez-Cintas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Barral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso C.","family":"Abad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Erikson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan E.","family":"Wineinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e0rbara","family":"Torrico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3","family":"Arenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquel","family":"Casas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ribas\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bru","family":"Cormand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e8lia","family":"Fern\u00e0ndez-Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,8]]},"reference":[{"key":"BFsrep31033_CR1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1192\/bjp.173.4.345","volume":"173","author":"KS Kendler","year":"1998","unstructured":"Kendler, K. 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