Genetic association of the AKT1 gene with schizophrenia in a British population.
OBJECTIVE
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 10000 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).


CONCLUSIONS
The present results provide further evidence to support the AKT1 association with schizophrenia.
Mathur
Aditi
A
The Genetics and Immunology Group, Department of Diabetes and Cardiovascular Science, UHI Millennium Institute, Inverness bSchool of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Law
Matthew H
MH
Megson
Ian L
IL
Shaw
Duncan J
DJ
Wei
Jun
J
D000328:Adult; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*; D006113:United Kingdom
C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt