For major depressive disorder (MDD), BDNF and GSK3B are logical candidate genes and an interaction between BDNF polymorphism and negative life events has been observed. Our previous study revealed that a gene-gene interaction among BDNF and GSK3B may confer the risk of MDD. In the present study, we hypothesized a gene-environment interaction between the BDNF-GSK3B combination and negative life events in the risk for developing MDD. To test this hypothesis, we conducted a case-control study in a northern Han Chinese population. A total of 404 patients with MDD and 388 age- and gender-matched control subjects were recruited. Negative life events and objective social supports were assessed using standard rating scales. Three polymorphisms of BDNF and GSK3B genes were identified by sequencing. Gene-environment interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). Under a dominant model, we observed a potential association between the GSK3B rs6782799 and MDD (P=0.07), a significant three-way interaction among BDNF rs6265, GSK3B rs6782799, and negative life events (corrected P-value, 0.011-0.012; cross-validation consistency, 7; prediction error, 0.4349). To our knowledge, this is the first report of evidence that the BDNF-GSK3B interaction may modify the relationship between negative life events and MDD in the Chinese population.
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