OBJECTIVE: Previous research has shown conflicting results for the significance of five v-akt murine thymoma viral oncogene homolog 1 (AKT1) single-nucleotide polymorphisms (SNPs) to the aetiology of schizophrenia. Neurocognition is a plausible endophenotype for schizophrenia and it was reasoned that the lack of agreement might be due to variability in neurocognition across studies. Therefore, the association of genetic variation in AKT1 with neurocognition was investigated in patients with schizophrenia. METHODS: The same five SNPs used in previous studies of the etiology of schizophrenia (rs2494732, rs2498799, rs3730358, rs1130214, [corrected] and rs3803300) were genotyped in 641 individuals with schizophrenia who had participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. The primary dependent variable was a neurocognitive composite score and exploratory analyses investigated five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance). RESULTS: There were no significant asymptotic or empirical associations between any SNP and the neurocognitive composite score. The authors also investigated the association of five-SNP haplotypes with the neurocognitive composite score. A marginally significant association was observed for the neurocognitive composite score with one of the five-SNP haplotypes (global score statistic 19.51, df = 9, permutation p = 0.02). Exploratory analyses of five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance) were non-significant for all five SNPs. CONCLUSION: Results published to date for an association between genetic variation in AKT1 with schizophrenia are inconsistent. The results suggest that the AKT1 markers studied are not associated with neurocognition in schizophrenia, and do not support unassessed variation in neurocognitive scores as a reason for this discrepancy.
OBJECTIVE: Previous research has shown conflicting results for the significance of five v-akt murinethymoma viral oncogene homolog 1 (AKT1) single-nucleotide polymorphisms (SNPs) to the aetiology of schizophrenia. Neurocognition is a plausible endophenotype for schizophrenia and it was reasoned that the lack of agreement might be due to variability in neurocognition across studies. Therefore, the association of genetic variation in AKT1 with neurocognition was investigated in patients with schizophrenia. METHODS: The same five SNPs used in previous studies of the etiology of schizophrenia (rs2494732, rs2498799, rs3730358, rs1130214, [corrected] and rs3803300) were genotyped in 641 individuals with schizophrenia who had participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. The primary dependent variable was a neurocognitive composite score and exploratory analyses investigated five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance). RESULTS: There were no significant asymptotic or empirical associations between any SNP and the neurocognitive composite score. The authors also investigated the association of five-SNP haplotypes with the neurocognitive composite score. A marginally significant association was observed for the neurocognitive composite score with one of the five-SNP haplotypes (global score statistic 19.51, df = 9, permutation p = 0.02). Exploratory analyses of five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance) were non-significant for all five SNPs. CONCLUSION: Results published to date for an association between genetic variation in AKT1 with schizophrenia are inconsistent. The results suggest that the AKT1 markers studied are not associated with neurocognition in schizophrenia, and do not support unassessed variation in neurocognitive scores as a reason for this discrepancy.
Authors: Anna C Need; Richard S E Keefe; Dongliang Ge; Iris Grossman; Sam Dickson; Joseph P McEvoy; David B Goldstein Journal: Eur J Hum Genet Date: 2009-01-21 Impact factor: 4.246
Authors: Olli P H Pietiläinen; Tiina Paunio; Anu Loukola; Annamari Tuulio-Henriksson; Tuula Kieseppä; Paul Thompson; Arthur W Toga; Theo G M van Erp; Karri Silventoinen; Pia Soronen; William Hennah; Joni A Turunen; Juho Wedenoja; Outi M Palo; Kaisa Silander; Jouko Lönnqvist; Jaakko Kaprio; Tyrone D Cannon; Leena Peltonen Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-07-05 Impact factor: 3.568
Authors: Scott A Langenecker; Erika F H Saunders; Allison M Kade; Michael T Ransom; Melvin G McInnis Journal: J Affect Disord Date: 2009-10-01 Impact factor: 4.839