The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population

Background: Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. Method: To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 Lag single nucleotide polymorphisms using TagMan (R) technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. Results: We found rs334535 (P-allele=2.79E-03, P-genotype=5.00E 03, OR=1.429) and rs2199503 (P-allele=0.020, P-genotype= 0.040, OR 1,157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted P - =1.64E-03, adjusted P-genotype=6.00E 03, 0R=0.701) and rs2199503 (adjusted P-allele=0.001, adjusted P-genotype = 0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted P-allele=1.70E-03, adjusted P-genotype=0.006, OR-1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Limitations: Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. Conclusions: Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references. (C) 2015 Published by Elsevier B.V.