Study Report

Reference	Karege, F.,2012 PMID: 22277669
Citation	Karege, F., A. Meary, et al. (2012). "Genetic overlap between schizophrenia and bipolar disorder: a study with AKT1 gene variants and clinical phenotypes." Schizophr Res 135(1-3): 8-14.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	364 patients suffering from SCZ(n=102), BPD(n=198) or schizoaffective disorder(n=64) and 165 healthy controls.
SNP/Region/Marker Size	6 SNPs
Predominant Ethnicity	Caucasian
Population	Swiss and French

Sample Diagnosis	DSM
Sample Status	All subjects were of West European origin: 364 patients were recruited from Switzerland (Geneva and Lausanne Hospitals) and France (Paris, Criteil Hospital centre). All patients met the criteria of DSM-IV (Diagnostic and Statistical Manual) (Amercican Psychiatric Association), either for schizophrenia, schizoaffective, bipolar depression type 1 or bipolar depression type 2. 165 unrelated healthy subjects (recruited from both centers) were used as controls. We subdivided the patients' sample into four groups according to the presence of mood symptoms (Group 1), psychotic symptoms only (group 4) and mixed symptoms but with different importance of mood and psychotic symptomatology (Group 2 and 3):- Group 1 includes BPD-I and BPD-II patients, without psychotic features. - Group 2 includes BPD-I and BPD-II patients, with mood-congruent psychotic features, as delusional excessive or inappropriate guilt every day. - Group 3 includes patients diagnosed as SCA ( at least psychotic symptoms for the majority of a one-month period and delusions or hallucinations present for a minimum of two weeks, without major mood symptoms).- Group 4 includes patients referred as SCZ with no personal history of mood disorder.
Technique	Genotyping
Statistical Method	Analyses for allelic and haplotype association were also performed with PLINK software.Data were combined both using a fixed effects (Mantel-Haenszel) model and a random effects model (DerSimonian and Laird estimator of the between study variance). Cochran's Q statistic and the I2 statistic were used to test and measure the presence and degree of between-study heterogeneity. The I2 metric has the advantage that it is independent of the number of studies and can be compared across meta-analyses with different numbers of studies and metrics. Values over 50% indicate great heterogeneity.
Result Summary	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. CONCLUSION: 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.