title: Cognitive endophenotypes inform genome-wide expression profiling in schizophrenia.
abstract: OBJECTIVE
  We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia.
  
  
  METHODS
  Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with the California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed.
  
  
  RESULTS
  After Bonferroni correction (p < 2.69 × 10-6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophrenia patients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies.
  
  
  CONCLUSIONS
  Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function.
authors.affiliation: Department of Psychology, Yale University.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Zheutlin
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Viehman
authors.affiliation: Department of Psychology, Yale University.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fortgang
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles.
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: National Institute for Health and Welfare.
authors.forename: Jaana
authors.identifier: 0000-0001-7167-0990
authors.initials: J
authors.lastname: Suvisaari
authors.affiliation: National Institute for Health and Welfare.
authors.forename: Sebastian
authors.identifier: 0000-0001-9407-4905
authors.initials: S
authors.lastname: Therman
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
authors.affiliation: Department of Psychology, Yale University.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D058068:Endophenotypes; D005260:Female; D005387:Finland; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008568:Memory; D046228:Microarray Analysis; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D012042:Registries; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D013548:Sweden; D014427:Twins / Q000235:genetics / Q000523:psychology
chemical_list: D012313:RNA