Possible association of different G72/G30 SNPs with mood episodes and persecutory delusions in bipolar I Romanian patients

The G72/G30 gene is one of the common loci shared both by schizophrenia and bipolar disorder. Studies accumulating since the discovery of this gene complex produced controversial results in both disorders in different populations. Objective: We investigated the association between the G72/. G30 gene and bipolar I disorder (BPI) in the Romanian population paying special attention to the association of G72/. G30 with lifetime psychosis and in particular with persecutory delusions in BPI patients. Method: Fourteen G72/G30-SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis was performed with FAMHAP and HAPLOVIEW-v3.32. The significance level of the results was corrected through permutations in 100,000 simulations. Results: None of the fourteen SNPs was associated with the global diagnosis of BPI in our total patient sample or with the psychotic BPI subtype. When confining the psychotic phenotype to persecutory delusions, we observed trends to association for SNPs previously associated with schizophrenia and persecutory delusions in BPI [M21 (P=0.080); M22 (P=0.092; P=0.042 under dominant transmission model); M24 (P=0.092)]. Four SNPs reached nominal significance in the non-psychotic BPI subgroup [rs3916965 (M12) (P=0.044), rs1935057 (P=0.037), rs3916967 (M14) (P=0.043), and rs2391191 (M15, non-synonymous) (P=0.043)]. After correction through permutations, the haploblock GA including M14 and M15 showed a trend to association with BPI (P=0.0524; OR=1.82) in the non-psychotic BPI subgroup. Conclusion: We report a potential association of different G72/G30-SNPs with non-psychotic mood episodes and with persecutory delusions in BPI Romanian patients. The results represent a first partial replication of two studies: Williams et al. (2006) and Schulze et al. (2005). The results have just a suggestive value since the Bonferroni correction for multiple testing was not applied.