title: Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Interdepartmental Neuroscience Program, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Lazaro
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Fuying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Interdepartmental Neuroscience Program, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Alden
authors.initials: A
authors.lastname: Huang
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Chow
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America; Department of Neurology, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America; Department of Neurology, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America; Department of Psychology, University of California Los Angeles, Los Angeles, United States of America.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
mesh_terms: D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D055028:Comparative Genomic Hybridization / Q000379:methods; D004062:DiGeorge Syndrome / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000235:genetics*