title: The combined effects of the BDNF and GSK3B genes modulate the relationship between negative life events and major depressive disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3