Genetic association of the AKT1 gene with schizophrenia in a British population

Objectives A number of studies have reported a genetic association of the AKT1 gene with schizophrenia, although some have failed to replicate the AKT1 association. This study was undertaken to further explore the AKT1 association with more single nucleotide polymorphisms in a British sample. Methods A total of 221 families, consisting of 148 fathers, 204 mothers and 222 offspring affected with schizophrenia, were recruited for genetic analysis. Analysis for allelic and haplotypic associations was performed with the UNPHASED program, using likelihood-based association analysis for nuclear families with missing parental genotype data. Results Allelic association was detected at rs1130214 (chi(2) = 6.28, P = 0.012) and at rs11847866 (chi(2) = 4.64, P = 0.031), although the remaining single nucleotide polymorphisms did not show allelic association with schizophrenia. The global P value of overall associations was 0.059 after 10 000 permutations. Assessment using the Haploview program revealed rs1130214, rs2494746 and rs11847866 in the same linkage disequilibrium block and haplotype analysis showed disease association for the rs1130214-rs2494746-rs11847866 haplotypes (chi(2) = 10.18, d.f. = 4, P = 0.037), of which the T-G-A haplotype was excessively transmitted (chi(2) = 6.93, uncorrected P = 0.008) and this haplotypic association survived Bonferroni correction (P = 0.04). Conclusion The present results provide further evidence to support the AKT1 association with schizophrenia. Psychiatr Genet 20:118-122 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.