title: Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants.
abstract: We searched a gene expression dataset comprised of 634 schizophrenia (SZ) cases and 713 controls for expression outliers (i.e., extreme tails of the distribution of transcript expression values) with SZ cases overrepresented compared with controls. These outlier genes were enriched for brain expression and for genes known to be associated with neurodevelopmental disorders. SZ cases showed higher outlier burden (i.e., total outlier events per subject) than controls for genes within copy number variants (CNVs) associated with SZ or neurodevelopmental disorders. Outlier genes were enriched for CNVs and for rare putative regulatory variants, but this only explained a small proportion of the outlier subjects, highlighting the underlying presence of additional genetic and potentially, epigenetic mechanisms.
authors.affiliation: Center for Psychiatric Genetics and Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA, jduan@uchicago.edu jduan@northshore.org.
authors.forename: Jubao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Center for Psychiatric Genetics and Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Sanders
authors.affiliation: Center for Psychiatric Genetics and Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: Winton
authors.initials: W
authors.lastname: Moy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA and.
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Drigalenko
authors.affiliation: Center for Biomedical Research Informatics, NorthShore University HealthSystem, Evanston, IL, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Brown
authors.affiliation: Center for Psychiatric Genetics and.
authors.forename: Jessica
authors.initials: J
authors.lastname: Freda
authors.affiliation: Center for Psychiatric Genetics and.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leites
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA and.
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.affiliation: Center for Psychiatric Genetics and Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Gejman
mesh_terms: D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome