title: Genetic overlap between schizophrenia and bipolar disorder: a study with AKT1 gene variants and clinical phenotypes.
abstract: BACKGROUND
  A number of epidemiological and genetic studies suggests an overlap of Schizophrenia and Bipolar disorder across the traditional binary classification. AKT1 gene variants were previously shown to be associated with schizophrenia. In this study, our aim was to determine whether AKT1 gene variants are associated with particular phenotypes for schizophrenia (SCZ) and bipolar disorder (BPD).
  
  
  METHODS
  This study included 529 subjects of European ancestry: 364 patients suffering from SCZ, BPD or schizoaffective disorder and 165 healthy controls. BPD patients were additionally subdivided into two groups: BPD with or without psychosis. Six AKT1 variants were assessed in a case-control study and allelic associations were analyzed. Moreover, meta-analyses were performed for those variants found in case-control studies of schizophrenia and schizoaffective disorder.
  
  
  RESULTS
  Nominal associations were found for three AKT1 gene variants, namely rs3803300, rs2494732 and rs2498804, in the four phenotypes. Two SNP survived Bonferroni corrections for multiple testing: rs3803300 (p<0.001) and rs2498804 (p<0.03) in group 1 (BPD without psychosis). In group 2 (BPD with psychosis) and in group 4 (SCZ), rs3803300 was significant but did not survive multiple testing. While rs2494732 was associated with the presence of psychosis (group-2, 3 and 4), rs2498804 was associated with affective symptoms (groups-1, 2 and 3). One meta-analysis found a significant level of association between rs3803300 and schizophrenia in Asian subjects.
  
  
  CONCLUSIONS
  AKT1 gene variations appeared to impact the risk for a class of psychiatric symptoms, comprising SCZ and BPD. Our findings support the view that AKT1 genetic variants are shared by both BPD and SCZ.
authors.affiliation: Geneva University Hospitals, Department of Medical Genetics and Laboratory; ch Petit Bel-Air 2;1225 Chêne-Bourg, Switzerland. felicien.karege@unige.ch
authors.forename: Félicien
authors.initials: F
authors.lastname: Karege
authors.forename: Alexandre
authors.initials: A
authors.lastname: Méary
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jamain
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Eladia
authors.initials: E
authors.lastname: Ballmann
authors.forename: Raphael
authors.initials: R
authors.lastname: Fernandez
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
authors.forename: Franck
authors.initials: F
authors.lastname: Schürhoff
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics*; D044465:White People
chemical_list: C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt