Rare genome-wide copy number variation and expression of schizophrenia in 22q11.2 deletion syndrome
| Autor: | Bassett, Anne S, Lowther, Chelsea, Merico, Daniele, Costain, Gregory, Chow, Eva WC, van Amelsvoort, Therese, McDonald-McGinn, Donna, Gur, Raquel E, Swillen, Ann, Van den Bree, Marianne, Murphy, Kieran, Gothelf, Doron, Bearden, Carrie E, Eliez, Stephan, Kates, Wendy, Philip, Nicole, Sashi, Vandana, Campbell, Linda, Vorstman, Jacob, Cubells, Joseph, Repetto, Gabriela M, Simon, Tony, Boot, Erik, Heung, Tracy, Evers, Rens, Vingerhoets, Claudia, van Duin, Esther, Zackai, Elaine, Vergaelen, Elfi, Devriendt, Koen, Vermeesch, Joris R, Owen, Michael, Murphy, Clodagh, Michaelovosky, Elena, Kushan, Leila, Schneider, Maude, Fremont, Wanda, Busa, Tiffany, Hooper, Stephen, McCabe, Kathryn, Duijff, Sasja, Isaev, Karin, Pellecchia, Giovanna, Wei, John, Gazzellone, Matthew J, Scherer, Stephen W, Emanuel, Beverly S, Guo, Tingwei, Morrow, Bernice E, Marshall, Christian R, International 22q11.2DS Brain and Behavior Consortium |
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| Přispěvatelé: | Eliez, Stéphan, Schneider, Maude, MUMC+: MA Med Staf Spec Psychiatrie (9), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Promovendi MHN |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Autism Spectrum Disorder CHILDHOOD Chromosome Disorders VARIANTS Genome Medical and Health Sciences ddc:616.89 0302 clinical medicine CHROMOSOMAL MICROARRAY DiGeorge syndrome 2.1 Biological and endogenous factors Copy-number variation Aetiology Genetics RISK Pediatric Psychiatry Middle Aged Serious Mental Illness Psychiatry and Mental health Mental Health Schizophrenia Female Chromosome Deletion BURDEN INTEGRATION Human Biotechnology Adult Psychosis 22q11 Deletion Syndrome DNA Copy Number Variations DISORDERS Velocardiofacial Syndrome Biology MICRODUPLICATIONS behavioral disciplines and activities Chromosomes MECHANISMS 03 medical and health sciences Clinical Research Intellectual Disability mental disorders medicine DiGeorge Syndrome Humans Autistic Disorder Gene MUTATIONS Pair 16 Prevention Human Genome Psychology and Cognitive Sciences Structural Variants Chromosome medicine.disease Brain Disorders 030104 developmental biology Microdeletion 030217 neurology & neurosurgery Chromosomes Human Pair 16 International 22q11.2DS Brain and Behavior Consortium |
| Zdroj: | American Journal of Psychiatry, 174(11), 1054 The American journal of psychiatry, vol 174, iss 11 American Journal of Psychiatry, 174(11), 1054. American Psychiatric Association American Journal of Psychiatry (2017) P. appiajp201716121417 American Journal of Psychiatry, 174(11), 1054-1063. American Psychiatric Publishing, Inc. |
| ISSN: | 0002-953X |
| Popis: | 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 assessedwhether 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. |
| Databáze: | OpenAIRE |
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