BACKGROUND: Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test. METHODS: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP. RESULTS: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association. CONCLUSIONS: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.
BACKGROUND: Abnormality of the V-akt murinethymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test. METHODS: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP. RESULTS: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association. CONCLUSIONS: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.
Authors: Giuseppe Blasi; Francesco Napolitano; Gianluca Ursini; Paolo Taurisano; Raffaella Romano; Grazia Caforio; Leonardo Fazio; Barbara Gelao; Annabella Di Giorgio; Luisa Iacovelli; Lorenzo Sinibaldi; Teresa Popolizio; Alessandro Usiello; Alessandro Bertolino Journal: Proc Natl Acad Sci U S A Date: 2010-12-27 Impact factor: 11.205
Authors: H Dong; M V Martin; J Colvin; Z Ali; L Wang; L Lu; R W Williams; G D Rosen; J G Csernansky; J M Cheverud Journal: Heredity (Edinb) Date: 2007-04-04 Impact factor: 3.821
Authors: Brennan T Harmon; Stephanie A Devaney; Heather Gordish-Dressman; Erica K Reeves; Po Zhao; Joseph M Devaney; Eric P Hoffman Journal: Hum Genet Date: 2010-09-26 Impact factor: 4.132
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Sarah S Murray; Kristin S Cadenhead; Monica E Calkins; Dorcas J Dobie; Michael F Green; Raquel E Gur; Ruben C Gur; Gary Hardiman; John R Kelsoe; Sherry Leonard; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Robert Freedman; David L Braff Journal: Am J Psychiatry Date: 2011-04-15 Impact factor: 18.112
Authors: Jennifer A McKenzie; Sarah Witkowski; Andrew T Ludlow; Stephen M Roth; James M Hagberg Journal: Exp Physiol Date: 2010-11-19 Impact factor: 2.969
Authors: Darrick T Balu; Gregory C Carlson; Konrad Talbot; Hala Kazi; Tiffany E Hill-Smith; Rachel M Easton; Morris J Birnbaum; Irwin Lucki Journal: Hippocampus Date: 2010-11-03 Impact factor: 3.899
Authors: Bernard Masri; Ali Salahpour; Michael Didriksen; Valentina Ghisi; Jean-Martin Beaulieu; Raul R Gainetdinov; Marc G Caron Journal: Proc Natl Acad Sci U S A Date: 2008-09-03 Impact factor: 11.205
Authors: Dawn L Thiselton; Vladimir I Vladimirov; Po-Hsiu Kuo; Joseph McClay; Brandon Wormley; Ayman Fanous; Francis A O'Neill; Dermot Walsh; Edwin J C G Van den Oord; Kenneth S Kendler; Brien P Riley Journal: Biol Psychiatry Date: 2007-09-06 Impact factor: 13.382