10.1371/journal.pone.0132542 Maria Jalbrzikowski Maria Jalbrzikowski Maria T. Lazaro Maria T. Lazaro Fuying Gao Fuying Gao Alden Huang Alden Huang Carolyn Chow Carolyn Chow Daniel H. Geschwind Daniel H. Geschwind Giovanni Coppola Giovanni Coppola Carrie E. Bearden Carrie E. Bearden Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder Public Library of Science 2015 idiopathic psychosis expression changes antipsychotic medication use risk factors 22 q 11.2 Deletion Syndrome response pathways WGCNA analyses ht transcriptional regulation idiopathic ASD.ConclusionThese findings Functional Pathways Related brain tissue 22 q 11DS patients gene idiopathic schizophrenia 22 q 11DS peripheral blood deletion characteristics 22 q 11DS individuals pathways dysregulated 22 q 11DS carriers module Transcriptome Profiling 3 Mb deletion data mining techniques deletion breakpoints de Genomic Analyses phenotypic variation aCGH array spectrum disorders transcriptional changes 2015-07-22 03:02:56 Dataset https://plos.figshare.com/articles/dataset/_Transcriptome_Profiling_of_Peripheral_Blood_in_22q11_2_Deletion_Syndrome_Reveals_Functional_Pathways_Related_to_Psychosis_and_Autism_Spectrum_Disorder_/1491728 <div><p>Background</p><p>22q11.2 Deletion Syndrome (22q11DS) represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD) in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes.</p><p>Methods</p><p>We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential expression (DE) and networks of co-expressed genes related to phenotypic variation within 22q11DS patients. Whole-genome transcriptional profiling was performed using Illumina Human HT-12 microarrays. Data mining techniques were used to validate our results against independent samples of both peripheral blood and brain tissue from idiopathic psychosis and ASD cases.</p><p>Results</p><p>Eighty-five percent of 22q11DS individuals (N = 39) carried the typical 3 Mb deletion, with significant variability in deletion characteristics in the remainder of the sample (N = 7). DE analysis and weighted gene co-expression network analysis (WGCNA) identified expression changes related to psychotic symptoms in patients, including a module of co-expressed genes which was associated with psychosis in 22q11DS and involved in pathways associated with transcriptional regulation. This module was enriched for brain-expressed genes, was not related to antipsychotic medication use, and significantly overlapped with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE and WGCNA analyses implicated dysregulation of immune response pathways. The ASD-associated module showed significant overlap with genes previously associated with idiopathic ASD.</p><p>Conclusion</p><p>These findings further support the use of peripheral tissue in the study of major mutational models of diseases affecting the brain, and point towards specific pathways dysregulated in 22q11DS carriers with psychosis and ASD.</p></div>