This haplotype showed higher frequencies in SZ (P = 0.021) and in BP (P = 0.0075) patients than in controls (Table 3). Interestingly, when all patients were pooled together, this risk haplotype remained significant (P = 0.0016) and held after Bonferroni corrections. To strengthen the power of our analysis and to highlight at-risk haplotypes, the analysis was then repeated with haplotypes formed by two-marker combinations excluding rs3813065. Inhibitors,research,lifescience,medical Omnibus tests showed

more significant P-values in combined SZ and BP patients compared to controls (omnibus test: P = 0.0032, X2 = 23.11, df = 8). SZ only and BP only versus controls showed the same tendency (omnibus tests: P = 0.0084, X2 = 17.25, df = 6 and P = 0.017, X2 = 17.09, df = 7, respectively). Moreover, even after corrections for multiple testing, one main haplotype (CA)13-G was more frequent in the pooled population Inhibitors,research,lifescience,medical of SZ and BD patients than in controls (P = 5.81 × 10−4). This risk haplotype was also statistically significant in SZ patients (P

= 0.0011) and showed a trend of association in Inhibitors,research,lifescience,medical BD patients (P = 0.022). Table 3 Haplotype analysis of the PIK3C3 gene in bipolar disorder (BD) and schizophrenia (SZ) As multiple positive findings were expected and found, the FDR q-value was calculated to quantify the joint probability of multiple findings reflecting true associations as opposed to false positives, taking into account all comparisons performed to test the three hypotheses. The three top associations of the Inhibitors,research,lifescience,medical multiple comparisons (Table 2) were attributed a q-value of 0.09 or less. While, after multiple comparison corrections, it was not possible to reject all of the null 4��8C manufacturer hypotheses at a conventional level of statistical significance, all three of them were very unlikely to represent Inhibitors,research,lifescience,medical false positives. Interaction analysis between PIK3C3 and BDNF variants After the omnibus test, one interaction remained statistically significant between rs6265 (BDNF) and rs8095411 (PIK3C3) in SZ compared to controls (omnibus test: P = 0.04637, X2 = 3.968, df = 1). This result is mainly supported by Oxymatrine genotype interaction rs6265/ rs8095411 A/G-A/G (16.46%

vs. 6.8%, P = 0.028). This interaction did not survive the Bonferroni test for multiple corrections. Discussion The aim of this case-control study was to assess the potential role of PIK3C3 genetic variants in SZ and BD patients and its possible interaction with a BDNF polymorphism. The analysis of the single marker yields a difference, albeit modest, in allele distribution of the rs3813065 (-432C>T) with respect to BD, but not SZ. This result replicates the previous study from Stopkova et al. (2004). Moreover, the minor allele distribution is similar to that described in previous publications, which reported that it was very rare in USA and Czech populations while homozygote was missing in Jewish populations in Israel (Stopkova et al. 2004).