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European Archives of Psychiatry and Clinical Neuroscience

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18.04.2017 | Original Paper

Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples

verfasst von: Julio Rodríguez-López, Beatriz Sobrino, Jorge Amigo, Noa Carrera, Julio Brenlla, Santiago Agra, Eduardo Paz, Ángel Carracedo, Mario Páramo, Manuel Arrojo, Javier Costas

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 6/2018

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Abstract

Copy number variants (CNVs) conferring risk of schizophrenia present incomplete penetrance, suggesting the existence of second genetic hits. Identification of second hits may help to find genes with rare variants of susceptibility to schizophrenia. The aim of this work was to search for second hits of moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the relevant genes in additional samples. To this end, ten patients with risk CNVs at cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole-exome sequencing. Rare single nucleotide variants, defined as those absent from main public databases, were classified according to bioinformatic prediction of pathogenicity by CADD scores. The average number of rare predicted pathogenic variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare predicted pathogenic variants in more than one sample. Follow-up resequencing of these genes in 432 additional cases and 432 controls identified a significant excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking into account its function in clathrin-mediated synaptic vesicle endocytosis at presynaptic terminals, our results suggest an impairment of this process in schizophrenia.

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Titel: Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples
verfasst von: Julio Rodríguez-López
Beatriz Sobrino
Jorge Amigo
Noa Carrera
Julio Brenlla
Santiago Agra
Eduardo Paz
Ángel Carracedo
Mario Páramo
Manuel Arrojo
Javier Costas
Publikationsdatum: 18.04.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 6/2018
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-017-0799-5

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Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples

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