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Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome

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dc.contributor.author Bassett, Anne
dc.contributor.author Lowther, Chelsea
dc.contributor.author Merico, Daniele
dc.contributor.author Costain, Gregory
dc.contributor.author Chow, Eva
dc.contributor.author van Amelsvoort, Therese
dc.contributor.author McDonald-McGinn, Donna
dc.contributor.author Gur, Raquel
dc.contributor.author Swillen, Ann
dc.contributor.author Van den Bree, Marianne
dc.contributor.author Murphy, Kieran
dc.contributor.author Gothelf, Doron
dc.contributor.author Bearden, Carrie
dc.contributor.author Eliez, Stephan
dc.contributor.author Kates, Wendy
dc.contributor.author Philip, Nicole
dc.contributor.author Sashi, Vandana
dc.contributor.author Campbell, Linda
dc.contributor.author Vorstman, Jacob
dc.contributor.author Cubells, Joseph
dc.contributor.author Repetto, Gabriela
dc.contributor.author Simon, Tony
dc.contributor.author Boot, Erik
dc.contributor.author Heung, Tracy
dc.contributor.author Evers, Rens
dc.contributor.author Vingerhoets, Claudia
dc.contributor.author van Duin, Esther
dc.contributor.author Zackai, Elaine
dc.contributor.author Vergaelen, Elfi
dc.contributor.author Devriendt, Koen
dc.contributor.author Vermeesch, Joris
dc.contributor.author Owen, Michael
dc.contributor.author Murphy, Clodagh
dc.contributor.author Michaelovosky, Elena
dc.contributor.author Kushan, Leila
dc.contributor.author Schneider, Maude
dc.contributor.author Fremont, Wanda
dc.contributor.author Busa, Tiffany
dc.contributor.author Hooper, Stephen
dc.contributor.author McCabe, Kathryn
dc.contributor.author Duijff, Sasja
dc.contributor.author Isaev, Karin
dc.contributor.author Pellecchia, Giovanna
dc.contributor.author Wei, John
dc.contributor.author Gazzellone, Matthew
dc.contributor.author Scherer, Stephen
dc.contributor.author Emanuel, Beverly
dc.contributor.author Guo, Tingwei
dc.contributor.author Morrow, Bernice
dc.contributor.author Marshall, Christian
dc.contributor.author International 22q11.2DS Brain and Behavior Consortium
dc.date.accessioned 2018-01-09T19:00:12Z
dc.date.available 2018-01-09T19:00:12Z
dc.date.issued 2017
dc.identifier.citation Am J Psychiatry. 2017 Nov 1;174(11):1054-1063 es_CL
dc.identifier.uri http://dx.doi.org/10.1176/appi.ajp.2017.16121417 es_CL
dc.identifier.uri http://hdl.handle.net/11447/1869
dc.description.abstract OBJECTIVE: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. METHOD: Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. RESULTS: Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. CONCLUSIONS: The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia. es_CL
dc.format.extent 10 es_CL
dc.language.iso en_US es_CL
dc.publisher American Psychiatric Association es_CL
dc.subject 22q11 Deletion Syndrome es_CL
dc.subject DiGeorge Syndrome es_CL
dc.subject Microdeletion es_CL
dc.subject Psychosis es_CL
dc.subject Schizophrenia es_CL
dc.subject Structural Variants es_CL
dc.subject Velocardiofacial Syndrome es_CL
dc.title Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome es_CL
dc.type Artículo es_CL


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