Genetic association of the interaction between the BDNF and GSK3B genes and major depressive disorder in a Chinese population

Alterations in brain-derived neurotrophic factor (BDNF)-signaling pathways may play an important role in the pathophysiology of major depressive disorder (MDD). Several lines of evidence have suggested that gene–gene interactions may confer susceptibility to MDD. The aim of this study was to analyze the single and combined effects of genes in the BDNF signal-transduction pathway on MDD in a Chinese population. We recruited 447 patients with MDD and 432 age- and gender-matched control subjects. Five SNPs in three BDNF signal-transduction pathway genes (BDNF, GSK3B and AKT1) were used in association analyses. An allelic association between the GSK3B SNP rs6782799 and MDD was found in our sample (allelic: χ² = 5.24, P = 0.022, corrected P = 0.107; genotypic: χ² = 5.55, P = 0.062) with an odds ratio (OR) of 1.25 (95% confidence interval (CI) 1.03–1.52). Further gene–gene interaction analyses showed a significant effect of a two-locus BDNF/GSK3B interaction with MDD (GSK3B rs6782799 and BDNF rs7124442) (corrected P = 0.011), and also for a three-locus interaction (GSK3B rs6782799, BDNF rs6265 and BDNF rs7124442) (corrected P = 0.019). Individuals carrying the combination of two risk alleles showed an OR value of 4.00 (95% CI 2.05–7.79), while those with the combination of three risk alleles gave the largest OR value of 4.46 (95% CI 2.15–9.24). Taken together, these findings support the assertion that the GSK3B gene is an important susceptibility factor for MDD in a Han Chinese population.